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Chemokines and Chemokine Receptors: New Targets for Cancer Immunotherapy

Valeria Mollica Poeta, Matteo Massara, Arianna Capucetti and 1 more

Frontiers in Immunology · 2019 · Review · CC BY

doi:10.3389/fimmu.2019.00379

Abstract

Immunotherapy is a clinically validated treatment for many cancers to boost the immune system against tumor growth and dissemination. Several strategies are used to harness immune cells: monoclonal antibodies against tumor antigens, immune checkpoint inhibitors, vaccination, adoptive cell therapies (e.g., CAR-T cells) and cytokine administration. In the last decades, it is emerging that the chemokine system represents a potential target for immunotherapy. Chemokines, a large family of cytokines with chemotactic activity, and their cognate receptors are expressed by both cancer and stromal cells. Their altered expression in malignancies dictates leukocyte recruitment and activation, angiogenesis, cancer cell proliferation, and metastasis in all the stages of the disease. Here, we review first attempts to inhibit the chemokine system in cancer as a monotherapy or in combination with canonical or immuno-mediated therapies. We also provide recent findings about the role in cancer of atypical chemokine receptors that could become future targets for immunotherapy.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 17, 2026. Paragraph numbers are ours, so an answer can point at one.

Role of Chemokines in Tumors

Inflammation is an essential component of the tumor microenvironment and one of the hallmarks of cancer. Chemokines, are a family of small, secreted, and structurally related cytokines with a crucial role in inflammation and immunity. They are also key mediators of cancer related inflammation being present at tumor site for pre-existing chronic inflammatory conditions but also being target of oncogenic pathways. Initially identified with a prominent role in determining the composition of tumor stroma, they were found able to directly affect cancer cell proliferation and metastasis.

Leukocyte Recruitment

The proper movement of immune cells is orchestrated by the spatial and temporal expression of chemokines. Inflammatory CC (CCL2, CCL3, CCL5) and CXC (CXCL1, CXCL2, CXCL5, CXCL6, and CXCL8) chemokines recruit at the tumor site CCR2+ monocytes and CXCR2+ neutrophils that differentiate into tumor associated macrophages (TAMs) and tumor associated neutrophils (TANs), exerting pro- or anti-tumoral role. Some chemokines present at tumor site can modify leukocyte activation, for instance CXCL16 acting on CXCR6 induces macrophage polarization toward a pro-tumoral phenotype in solid tumors. CXCL9 and CXCL10 are strongly associated with Th1 immune response by recruiting NK cells, CD4+ Th1 and CD8+ cytotoxic lymphocytes, which can elicit antitumoral responses. Moreover, potent attractant of dendritic cells (DC) are CCL20, CCL5, and CXCL12; CCL21 and CCL19 recruit CCR7+ DC but also regulatory T cells (Tregs). CCL17 and CCL22 acting on CCR4 can directly recruit Tregs and Th2 lymphocytes, that promote tumor growth and proliferation.

Angiogenesis

Both CC and CXC chemokines play a critical role in tumor angiogenesis, essential for tumor growth and metastatic spreading. CXC chemokines, based on the presence of glutamic-leucine-arginine (ELR) motif at the N-terminal, can be divided in ELR+ chemokines with angiogenic and ELR− chemokines with angiostatic effects. CCL2, CCL11, CCL16, CCL18, and CXCL8 promote tumor angiogenesis and endothelial cell survival. Moreover, CXCL16 interacting with CXCR6, acts as a potent angiogenic mediator. CXCL12 and CCL2 can promote angiogenesis and inhibit apoptosis of endothelial cells by directly binding their receptor (CXCR4 and CCR2, respectively) expressed on tumor vessels or indirectly promoting the recruitment of leukocytes. On the contrary, chemokines, such as CCL21 and ELR− chemokines (CXCL4, CXCL9, CXCL10, and CXCL11) inhibit angiogenesis and endothelial cell proliferation.

Tumor Growth and Proliferation

Chemokines produced by tumor itself, cancer-associated fibroblasts and infiltrating leukocytes, through the binding of chemokine receptors expressed by tumor cells, directly promote cancer cell proliferation activating different signaling pathways, such as PI3K/AKT/NF-κB and MAPK/ERK pathway. Additionally, they can promote tumor cell survival by preventing their apoptosis and regulating the balance between pro- and anti-apoptotic molecules (e.g., downregulation of Bcl-2 expression or inhibition of caspase-3 and caspase-9 activation).

Metastasis

Chemokine receptors expressed by cancer cells promote their migration to metastatic sites. Chemokines and chemokine receptors involved in this phenomenon are several: CCR7 mediates the migration of tumor cells to lymph nodes where their ligands, CCL19 and CCL21, are produced. The CCR10/CCL27 axis facilitates the adhesion and survival of melanoma cells during metastatic spreading. CCL28 promotes breast cancer growth and metastasis spreading through MAPK/ERK pathway. Finally the chemokine receptor CXCR5 and its ligand CXCL13 support bone metastases in prostate cancer. However, the main player of this process is the CXCL12/CXCR4 axis. In several tumors, CXCR4 expression endows cancer cells with the ability to migrate and metastasize into organs secreting high levels of CXCL12.

Chemokines in Cancer Therapy

Targeting the immune system represents a concrete approach against cancer. Starting from Coley's toxin development in 1893, many strategies have been set to enhance the antitumor activity of leukocytes. Given that chemokines and their receptors have been found involved in several aspects of cancer biology, their possible targeting was evaluated in many preclinical studies and clinical trials (Table 1 and Figure 1). Actually, a monoclonal antibody (anti-CCR4 mAb, Mogamulizumab) and a chemokine receptor inhibitor (CXCR4 antagonist AMD3100) are already in the clinical practice for hematological malignancies (see below).

CCR1

Inhibition of CCR1 reduces cancer growth and metastatization mainly by targeting myeloid cells. In mouse models of Multiple Myeloma (MM) the CCR1 antagonist CCX721 reduced tumor growth and osteolysis targeting osteoclasts and their precursors. The same effect was also given by blocking the CCR1 ligand CCL3 that is highly produced by MM cells. In a murine model of colon cancer liver metastasis, the CCR1 antagonist BL5923 inhibited metastasis by limiting the recruitment of immature myeloid cells. The CCR1 receptor antagonist CCX9588 was recently used in combination with anti-PD-L1 in a murine model of breast cancer showing a synergistic antitumoral effect by reducing the myeloid infiltrate. Due to the fact that CCR1 antagonists did not show adverse effects when used in autoimmune disease patients, they are ideal candidates to modulate the myeloid infiltrate in combination treatments.

CCR2 and CCL2

Interference with the CCL2/CCR2 axis exerts antitumoral activity in many cancers for the reduced recruitment of monocytes with pro-tumorigenic and pro-metastatic activities.

Many data are available in the context of pancreatic tumors. In a preclinical model, the oral CCR2 inhibitor PF-04136309 reduced the number of TAMs and exerted a modest effect on tumor growth when used alone, while it acted synergistically with the chemotherapeutic drug Gemcitabine (GEM). Encouraging results of a Phase Ib/II trial with pancreatic cancer patients, in which PF-04136309 is used in combination with nab-Paclitaxel [(PTX), a nanoparticle albumin-bound formulation of PTX able to induce TAM activation toward an M1 like phenotype], and GEM, were recently published (NCT02732938). The same inhibitor was used in another clinical trial (NCT01413022) performed on borderline resectable or locally advanced pancreatic ductal adenocarcinoma patients in combination with the standard chemotherapy FOLFIRINOX (FX). Preliminary results demonstrated that the combination therapy increased the percentage of objective responses. Another CCR2 inhibitor, CCX872, is really promising in the context of pancreatic tumors. In a preclinical setting, it improved the efficacy of the anti-PD-1 treatment and positive results were also obtained in a clinical trial (NCT02345408) when used in combination with FX. In murine models of hepatocellular carcinoma (HCC), CCR2 targeting with the antagonists RDC018 or 747 in combination with Sorafenib, reduced tumor growth and metastasis with a corresponding decrease in macrophage infiltration. In prostate and breast cancer, CCR2 was found expressed by tumor cells and to promote cancer growth and migration. However, targeting CCL2 with the humanized monoclonal CCL2 neutralizing antibody CNTO 888 in a phase I trial (NCT00537368) in solid tumors and in a phase II trial (NCT00992186) in metastatic prostate cancer, was unsuccessful due to ineffectiveness of CNTO 888 in reducing CCL2 serum level. More recent preclinical data indicated that in breast cancer models inhibition of CCL2 improved the response to radiotherapy and was effective in preventing metastasis, but its discontinuation caused a rebound in the number of circulating monocytes increasing metastatic spreading. Finally, in ovarian cancer, a CCR2 inhibitor enhanced peptide vaccination. All these data suggest that targeting the CCL2-CCR2 axis could be effective especially in combination therapies but attention has to be given to fluctuations in the number of circulating monocytes that can produce controversial effects.

CCR4

CCR4 is overexpressed in many hematologic malignancies such as Adult T-cell leukemia (ATL) and Cutaneous T-cell lymphoma (CTL). The human anti-CCR4 antibody Mogamulizumab eliminates tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and is actually in use in Japan for the treatment of relapsed/refractory ATL. It is also considered the best therapy for previously treated CTL patients according to an international phase III trial. In addition, in preclinical studies, CAR-T cells generated against CCR4, were found effective in the treatment of a wide spectrum of T cell malignancies.

CCR4 is also considered a promising target for solid tumors for its activity in modulating leukocyte infiltrate, in particular for depleting Tregs. In a preclinical model of renal cancer, Affi 5, a CCR4 blocking mAb, reduced tumor growth affecting the phenotype of myeloid cells and increasing the number of infiltrating NK cells. CCR4 is now considered a target for renal carcinoma patients. However, there are major concerns about the safety of the use of mAbs against CCR4 especially in patients previously subjected to allogenic bone marrow (BM) transplant. Anti-CCR4 mAbs are also depleting Tregs for few months, increasing the risk of graft-vs-host disease. For this reason, small molecule antagonists of CCR4 with less harmful side effects are in development and one of them, AF399/420/1802, considerably improved the efficacy of cancer vaccines in different preclinical tumor models (melanoma, lung, and colon cancer) by preventing Tregs induction.

CCR5

The role of CCR5 in cancer remains still controversial; depending on the cell type on which it is expressed it can have a pro- or anti-tumoral role. When expressed by tumor cells it drives their growth and metastatization, while when expressed by T cells potentiates anti-tumoral responses. For instance in breast cancer, a dual role of the receptor has been reported in promoting antitumor immune responses, but being also associated with cancer progression and metastasis. More recent data indicate that CCR5 induces the mobilization of myeloid cells with pro-tumoral activity and results obtained with preclinical and clinical models of colorectal cancer (CRC) indicate that targeting CCR5 with the negative allosteric inhibitor Maraviroc promoted the polarization of macrophages toward an antitumoral state. Very interestingly, objective partial response was reported in three out of five patients who received a combination of Maraviroc (NCT01736813) and chemotherapy. These data suggest that targeting CCR5 could have a major antitumoral effect on tumors that are CCR5 positive and have a prevalent myeloid infiltrate with immunosuppressive activity, while in other tumors CCR5 activity on T cells needs to be preserved for the correct development of the immune response.

CCR7

The therapeutic application of CCR7 inhibitors is also extremely promising. CCR7 is overexpressed by many tumors driving both tumor growth and metastatization. By the use of siRNA technology, CCR7 inhibition resulted in decreased number of metastasis in a model of colon carcinoma and inhibited the growth of prostate cancer. Moreover, reduction of CCR7 expression in breast cancer inhibited metastasis and single-chain antibodies blocking CCR7 (MSM R707) were found able to inhibit brain metastasis of T-cell acute lymphoblastic leukemia.

CXCR2

CXCR2 is expressed by many tumor cells and is involved in the chemotherapy resistance in different preclinical models of cancer. In breast cancer cells, CXCR2 deletion resulted in better response to Paclitaxel. In a melanoma model, the CXCR2 inhibitor Navarixin synergized with MEK inhibition whereas, in an ovarian tumor model, the CXCR2 inhibitor SB225002 improved the antiangiogenic therapy Sorafenib. Finally, in human gastric cancer, Reparixin, a CXCR1 and CXCR2 inhibitor, enhanced the efficacy of 5-fluorouracil.

CXCR2 targeting inhibits tumor growth also because it affects myeloid cell infiltration. In pancreatic tumors, CXCR2 inhibition prevented the accumulation of neutrophils unleashing the T cell response, resulting in inhibition of metastatic spreading and improved response to anti-PD-1. Interestingly, the combined treatment of CXCR2 and CCR2 inhibitors limited the compensatory response of TAMs, increased antitumor immunity and improved response to FX. Finally, in a prostate cancer model, CXCR2 inhibition by SB265610, decreased recruitment of myeloid cells and enhanced Docetaxel-induced senescence, limiting tumor growth.

Following these promising preclinical results, a phase II clinical trial with the CXCR2 inhibitor AZD5069 is ongoing in pancreatic cancer patients (NCT02583477). In addition, the safety of using Reparixin in combination with Paclitaxel was assessed and a double-blind study with these drugs for metastatic triple-negative breast cancer is in progress (NCT02370238).

CXCR4

The CXCR4 antagonist AMD3100 (Plerixafor) is clinically approved for the mobilization of hematopoietic stem cells (HSCs) for transplantation in patients with Non-Hodgkin's lymphoma (NHL) or MM. Beside the HSCs mobilization effect, many preclinical data and clinical trials with AMD3100 or other CXCR4 inhibitors are now suggesting their effectiveness in tumors.

Referring to hematological malignancies, some CXCR4 antagonists, like AMD3100 and the derivative AMD3465, enhanced the efficacy of conventional therapies inducing the mobilization of cancer cells from the protective environment of the BM. In murine models of AML, AMD3100 improved the efficacy of chemotherapy with Ara-C. Similar results were obtained in a phase I/II study in patients with relapsed AML. The CXCR4 antagonists LY2510924 was also able to suppress the proliferation and progression of AML used as monotherapy. Another CXCR4 antagonist, BKT140 had an anti-leukemic effect in a murine model of NHL and its action was synergic with Rituximab. Phase I trials are ongoing to evaluate the safety and tolerability of the anti-CXCR4 mAbs BMS-936564 in AML patients (NCT01120457) and PF-06747143 in hematological malignancies (NCT02954653).

CXCR4 inhibitors have strong antitumor and anti-metastatic effects also in solid tumors. In glioblastoma (GBM), CXCR4 expression is higher in more aggressive tumors and is further upregulated by anti-angiogenic therapies. AMD3465 reduced the growth of xenografts of glioblastoma multiforme and medulloblastoma cell lines and the CXCR4 antagonist PRX177561, increased the antitumor effects of Bevacizumab and Sunitinib in subcutaneous or orthotopic xenografts of glioblastoma models. The CXCR4 antagonist POL5551 inhibited GBM growth and dissemination after anti-VEGF therapy. Current clinical trials with AMD3100 in newly diagnosed or recurrent GBM patients are evaluating the safety and efficacy of daily subcutaneous injection (NCI2012-00149) or 2 weeks continuous intravenous infusion (NCI2013-02012). A phase I/II study of the CXCR4 antagonist USL311 alone and in combination with Lomustine is ongoing in patients with advanced solid tumors and relapsed/recurrent glioblastoma multiforme (NCT02765165).

In addition to brain tumors, AMD3465 and LY2510924 have been found to inhibit tumor growth and metastatization in many preclinical models. LY2510924, tested in a phase I trial (NCT02737072), was found clinically safe and well-tolerated in advanced solid cancers (colorectum, lung, breast, and prostate). A phase I trial (NCT01837095) of the CXCR4 antagonist Balixafortide plus Eribulin in HER2-negative metastatic breast cancer has given promising results.

Notably, CXCR4 inhibition is not only acting on tumor cells but is also promoting antitumoral T cell responses. In a pancreas tumor model, AMD3100, blocking the interaction of CXCR4 positive tumor cells with CXCL12 producing fibroblasts, unleashed a rapid accumulation of T cells and acted synergistically with anti-PD-L1. In a mesothelioma model, AMD3100 increased the efficiency of the vaccine against mesothelin (VIC-008) by inhibiting PD-1 expression on CD8 T cells and by converting Tregs in T helper like cells. The inhibition of Tregs infiltration and the promotion of antitumoral T cell response by AMD3100 were also demonstrated in a mouse model of ovarian cancer.

The Atypicals in the Immunotherapy Landscape

Atypical chemokine receptors (ACKRs) are emerging as crucial regulatory components of the chemokine network in a wide range of homeostatic and pathological conditions. In this section, we reported preclinical observations and clinical data that provide evidences on their importance in cancer biology suggesting the possibility to validate them as new targets for innovative immunotherapies.

ACKR1 is mainly expressed on post-capillary and small collecting venular endothelial cells (ECs) and red blood cells, but also in many tumors such as GBM, hemangiosarcoma, erythroleukemia, breast, and colorectal cancers. It is able to bind a broad panel of both CC and CXC inflammatory chemokines acting as chemokine transporter. However, its role remains unclear in cancer because when expressed by ECs promotes tumor growth generating a chemokine gradient that sustains leukocyte infiltration. On the contrary, ACKR1 was reducing tumor growth in a model of prostate cancer through the binding of angiogenic ELR+ CXC-chemokines that decreased angiogenesis and in a melanoma lung metastasis model, interacting with the tetraspanin CD82/KAI that induced tumor cells senescence. Finally, in breast carcinoma, ACKR1 expression correlated with a more favorable prognosis with less lymph nodes metastasis and better survival.

ACKR2 plays a non-redundant role in the control of inflammatory response by scavenging and degrading most inflammatory CC chemokines, acting as agonists for receptors from CCR1 to CCR5. It is expressed by trophoblast cells in placenta, lymphatic endothelial cells and at low levels by subsets of leukocytes. ACKR2 acts as a tumor extrinsic suppressor gene. Indeed, by dampening inflammation, it has a protective role in different inflammation-driven tumor models. ACKR2 prevents tumor growth also when it is expressed by Kaposi's sarcoma cells where it is down-regulated by the oncogenic pathway KRAS/BRAF/MEK/MAPK, while in anaplastic thyroid carcinomas ACKR2 expression is downregulated by miR-146a. In both tumors ACKR2 downregulation unleashes pro-tumoral leukocyte infiltration.

On the contrary, ACKR2 has a tumor promoting role in the Apc-Min model of CRC limiting mast cells infiltration and activation of CD8+ T cells and it has a pro-metastatic function in breast and melanoma cancer models, by limiting neutrophil and NK activity.

ACKR3, is a high affinity receptor for CXCL12 and CXCL11 expressed by hematopoietic cells, mesenchymal cells, activated ECs, and neurons. ACKR3 negatively regulates CXCL11 and CXCL12 bioavailability and modulates CXCR4 expression and function. In cancer, ACKR3 was found expressed on many tumor cells (such as renal carcinoma, breast cancer, and glioblastoma) and by tumoral ECs. It promotes tumor cell growth and metastasis acting on mTOR pathway. In lung adenocarcinoma, ACKR3 mediates TGF-ß1 promoted epithelial to mesenchymal transition (EMT) and tumor growth. ACKR3 is also expressed by aggressive prostate carcinoma cells and in renal carcinoma patients with decreased survival and poor prognosis. In renal cell carcinoma, ACKR3 expressed by endothelial progenitor cells and tumoral ECs exerts a proangiogenic role inducing their migration and survival. In a glioblastoma murine model, mice treated with X7Ab against ACKR3 in combination with Temozolomide (TMZ) showed significant tumor reduction and longer survival, enhancing M1 macrophage activation.

The last member of the family, ACKR4 is a scavenger receptor for CCL19, CCL21, CCL25, and CXCL13. It is expressed by keratinocytes, thymic epithelium and bronchial cells. Some papers indicated a protective role of ACKR4 in tumors. In HCC tumors, it impaired chemotactic events associated with CCR7, limiting tumor progression and metastasis. ACKR4 down-regulation in human breast and colon cancer correlated with a worse outcome. However, in breast carcinoma ACKR4 had a pro-metastatic role regulating EMT.

Concluding Remarks

Being chemokines and chemokine receptors expressed by both tumor cells and leukocyte infiltrate they represent an ideal target for immunotherapy. However, better understanding of their roles in different malignancies is still necessary to avoid potential side effects. In hematological malignancies targeting of overexpressed chemokine receptors directly kill tumor cells but can potentially induce unwanted immune reactions (e.g., CCR4).

In the context of solid tumors, chemokine receptor inhibitors are giving encouraging results when used in combination with chemotherapy or with antibodies against immune checkpoints. For this reason, it is possible to envisage that chemokine receptor inhibitors will be used in the future to modulate the stromal component, to overcome chemotherapy resistance and to optimize the immune response of the patients.

Author Contributions

VMP wrote the initial draft. AC, MM, and RB made substantial contributions and discussed the content. All authors reviewed and/or edited the manuscript prior submission.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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    Kitamura T Fujishita T Loetscher P Revesz L Hashida H Kizaka-Kondoh S. Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model. Proc Natl Acad Sci USA. (2010 ) 107:13063–8.

    Not in our library10.1073/pnas.1002372107

  47. 47.

    Jung H Bischof A Ebsworth K Ertl L Schall T Charo I Combination therapy of chemokine receptor inhibition plus PDL-1 blockade potentiates anti-tumor effects in a murine model of breast cancer. J Immunother Cancer. (2015 ) 3:P227

    Not in our library10.1186/2051-1426-3-s2-p227

  48. 48.

    Mitchem JB Brennan DJ Knolhoff BL Belt BA Zhu Y Sanford DE. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. (2013 ) 73:1128–41.

    Not in our library10.1158/0008-5472.can-12-2731

  49. 49.

    Noel M Lowery M Ryan D Wolpin B Bullock A Britten C 750PPhase Ib study of PF-04136309 (an oral CCR2 inhibitor) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic adenocarcinoma. Annals Oncol. (2017 ) 28(Suppl 5):209–68.

    Not in our library10.1093/annonc/mdx369.132

  50. 50.

    Jung H Ertl L Janson C Schall T Charo I Abstract A107, Inhibition of CCR2 potentiates the checkpoint inhibitor immunotherapy in pancreatic cancer. Cancer Immunol Res. (2016 ) 4(Suppl. 11):A107

    Not in our library10.1158/2326-6066.imm2016-a107

  51. 51.

    Nywening TM Wang-Gillam A Sanford DE Belt BA Panni RZ Cusworth BM. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer, a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. (2016 ) 17:651–62.

    Not in our library10.1016/s1470-2045(16)00078-4

  52. 52.

    Li X Yao W Yuan Y Chen P Li B Li J. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. (2017 ) 66:157–67.

    Not in our library10.1136/gutjnl-2015-310514

  53. 53.

    Linehan D Smith Noel M Hezel AF Wang-Gillam A Eskens F Sleijfer S Overall survival in a trial of orally administered CCR2 inhibitor CCX872 in locally advanced/metastatic pancreatic cancer, Correlation with blood monocyte counts. J Clin Oncol. (2018 ) 36:92

    Not in our library10.1200/jco.2018.36.5_suppl.92

  54. 54.
    A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer · 2017
    Not checked
  55. 55.

    Binder P Cullinan D Wilkinson-Ryan I Goedegebuure P Powell MA Mutch DG CCR2 blockade alters the tumor microenvironment immune infiltrate and enhances anti-tumor activity in ovarian cancer. Gynecol Oncol. (2017 ) 145:36

    Not in our library10.1016/j.ygyno.2017.03.094

  56. 56.

    Bonapace L Coissieux MM Wyckoff J Mertz KD Varga Z Junt T. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature. (2014 ) 515:130–3.

    Not in our library10.1038/nature13862

  57. 57.

    Pienta KJ Machiels JP Schrijvers D Alekseev B Shkolnik M Crabb SJ. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs. (2013 ) 31:760–8.

    Not in our library10.1007/s10637-012-9869-8

  58. 58.

    Sandhu SK Papadopoulos K Fong PC Patnaik A Messiou C Olmos D. A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol. (2013 ) 71:1041–50.

    Not in our library10.1007/s00280-013-2099-8

  59. 59.

    Perera LP Zhang M Nakagawa M Petrus MN Maeda M Kadin ME. Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies. Am J Hematol. (2017 ) 92:892–901.

    Not in our library10.1002/ajh.24794

  60. 60.

    Fuji S Utsunomiya A Inoue Y Miyagi T Owatari S Sawayama Y. Outcomes of patients with relapsed aggressive adult T-cell leukemia-lymphoma, clinical effectiveness of anti-CCR4 antibody and allogeneic hematopoietic stem cell transplantation. Haematologica. (2018 ) 103:e211–4.

    Not in our library10.3324/haematol.2017.184564

  61. 61.

    Berlato C Khan MN Schioppa T Thompson R Maniati E Montfort A. A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer. J Clin Invest. (2017 ) 127:801–13.

    Not in our library10.1172/jci82976

  62. 62.

    Beziaud L Boullerot L Tran T Mansi L Marie-Joseph EL Ravel P. Rapalog combined with CCR4 antagonist improves anticancer vaccines efficacy. Int J Cancer. (2018 ) 143:3008–18.

    Not in our library10.1002/ijc.31842

  63. 63.

    Rose S Mogamulizumab tops standard of care for CTCL. Cancer Discov. (2018 ) 8:1

    Not in our library10.1158/2159-8290.cd-nb2018-001

  64. 64.

    Halama N Zoernig I Berthel A Kahlert C Klupp F Suarez-Carmona M. Tumoral Immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell. (2016 ) 29:587–601.

    Not in our library10.1016/j.ccell.2016.03.005

  65. 65.

    Yu S Duan J Zhou Z Pang Q Wuyang J Liu T. A critical role of CCR7 in invasiveness and metastasis of SW620 colon cancer cell in vitro and in vivo. Cancer Biol Ther. (2008 ) 7:1037–43.

    Not in our library10.4161/cbt.7.7.6065

  66. 66.

    Chi BJ Du CL Fu YF Zhang YN Wang RW. Silencing of CCR7 inhibits the growth, invasion and migration of prostate cancer cells induced by VEGFC. Int J Clin Exp Pathol. (2015 ) 8:12533–40. Available online at: http://www.ijcep.com/files/ijcep0014636.pdf

    Not in our library

  67. 67.

    Micallef IN Stiff PJ Nademanee AP Maziarz RT Horwitz ME Stadtmauer EA. Plerixafor plus granulocyte colony-stimulating factor for patients with non-hodgkin lymphoma and multiple myeloma, long-term follow-up report. Biol Blood Marrow Transplant. (2018 ) 24:1187–95.

    Not in our library10.1016/j.bbmt.2018.01.039

  68. 68.

    Sharma B Nawandar DM Nannuru KC Varney ML Singh RK. Targeting CXCR2 enhances chemotherapeutic response, inhibits mammary tumor growth, angiogenesis, and lung metastasis. Mol Cancer Ther. (2013 ) 12:799–808.

    Not in our library10.1158/1535-7163.mct-12-0529

  69. 69.

    Young HL Rowling EJ Bugatti M Giurisato E Luheshi N Arozarena I. An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition. J Exp Med. (2017 ) 214:1691–710.

    Not in our library10.1084/jem.20160855

  70. 70.

    Schott AF Goldstein LJ Cristofanilli M Ruffini PA McCanna S Reuben JM. Phase Ib pilot study to evaluate reparixin in combination with weekly paclitaxel in patients with HER-2-negative metastatic breast cancer. Clin Cancer Res. (2017 ) 23:5358–65.

    Not in our library10.1158/1078-0432.ccr-16-2748

  71. 71.

    Devapatla B Sharma A Woo S. CXCR2 inhibition combined with sorafenib improved antitumor and antiangiogenic response in preclinical models of ovarian cancer. PLoS ONE. (2015 ) 10:e0139237.

    Not in our library10.1371/journal.pone.0139237

  72. 72.

    Wang J Hu W Wang K Yu J Luo B Luo G. Repertaxin, an inhibitor of the chemokine receptors CXCR1 and CXCR2, inhibits malignant behavior of human gastric cancer MKN45 cells in vitro and in vivo and enhances efficacy of 5-fluorouracil. Int J Oncol. (2016 ) 48:1341–52.

    Not in our library10.3892/ijo.2016.3371

  73. 73.

    Chao T Furth EE Vonderheide RH. CXCR2-dependent accumulation of tumor-associated neutrophils regulates T-cell immunity in pancreatic ductal adenocarcinoma. Cancer Immunol Res. (2016 ) 4:968–82.

    Not in our library10.1158/2326-6066.cir-16-0188

  74. 74.

    Steele CW Karim SA Leach JDG Bailey P Upstill-Goddard R Rishi L. CXCR2 Inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell. (2016 ) 29:832–45.

    Not in our library10.1016/j.ccell.2016.04.014

  75. 75.

    Nywening TM Belt BA Cullinan DR Panni RZ Han BJ Sanford DE. Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma. Gut. (2018 ) 67:1112–23.

    Not in our library10.1136/gutjnl-2017-313738

  76. 76.

    Di Mitri D Toso A Chen JJ Sarti M Pinton S Jost TR. Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer. Nature. (2014 ) 515:134–7.

    Not in our library10.1038/nature13638

  77. 77.

    Nervi B Ramirez P Rettig MP Uy GL Holt MS Ritchey JK. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood. (2009 ) 113:6206–14.

    Not in our library10.1182/blood-2008-06-162123

  78. 78.

    Uy GL Rettig MP Motabi IH McFarland K Trinkaus KM Hladnik LM A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. (2012 ) 119:3917–24.

    Not in our library10.1182/blood-2011-10-383406

  79. 79.

    Cho BS Zeng Z Mu H Wang Z Konoplev S McQueen T. Antileukemia activity of the novel peptidic CXCR4 antagonist LY2510924 as monotherapy and in combination with chemotherapy. Blood. (2015 ) 126:222–32.

    Not in our library10.1182/blood-2015-02-628677

  80. 80.

    Peng SB Zhang X Paul D Kays LM Gough W Stewart J. Identification of LY2510924, a novel cyclic peptide CXCR4 antagonist that exhibits antitumor activities in solid tumor and breast cancer metastatic models. Mol Cancer Ther. (2015 ) 14:480–90.

    Not in our library10.1158/1535-7163.mct-14-0850

  81. 81.

    Galsky MD Vogelzang NJ Conkling P Raddad E Polzer J Roberson S. A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer. Clin Cancer Res. (2014 ) 20:3581–8.

    Not in our library10.1158/1078-0432.ccr-13-2686

  82. 82.

    Beider K Ribakovsky E Abraham M Wald H Weiss L Rosenberg E. Targeting the CD20 and CXCR4 pathways in non-hodgkin lymphoma with rituximab and high-affinity CXCR4 antagonist BKT140. Clin Cancer Res. (2013 ) 19:3495–507.

    Not in our library10.1158/1078-0432.ccr-12-3015

  83. 83.

    Liu SH Gu Y Pascual B Yan Z Hallin M Zhang C. A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies. Blood Adv. (2017 ) 1:1088–100.

    Not in our library10.1182/bloodadvances.2016003921

  84. 84.

    Ling X Spaeth E Chen Y Shi Y Zhang W Schober W. The CXCR4 antagonist AMD3465 regulates oncogenic signaling and invasiveness in vitro and prevents breast cancer growth and metastasis in vivo. PLoS ONE. (2013 ) 8:e58426.

    Not in our library10.1371/journal.pone.0058426

  85. 85.

    Pham K Luo D Siemann DW Law BK Reynolds BA Hothi P. VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFbetaR signaling-dependent manner. Cancer Lett. (2015 ) 360:60–7.

    Not in our library10.1016/j.canlet.2015.02.005

  86. 86.

    Gagner JP Sarfraz Y Ortenzi V Alotaibi FM Chiriboga LA Tayyib AT. Multifaceted C-X-C chemokine receptor 4 (CXCR4) inhibition interferes with anti-vascular endothelial growth factor therapy-induced glioma dissemination. Am J Pathol. (2017 ) 187:2080–94.

    Not in our library10.1016/j.ajpath.2017.04.020

  87. 87.

    Righi E Kashiwagi S Yuan J Santosuosso M Leblanc P Ingraham R. CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res. (2011 ) 71:5522–34.

    Not in our library10.1158/0008-5472.can-10-3143

  88. 88.

    Pernas S Martin M Kaufman PA Gil-Martin M Gomez Pardo P Lopez-Tarruella S. Balixafortide plus eribulin in HER2-negative metastatic breast cancer, a phase 1, single-arm, dose-escalation trial. Lancet Oncol. (2018 ) 19:812–24.

    Not in our library10.1016/s1470-2045(18)30147-5

  89. 89.

    Feig C Jones JO Kraman M Wells RJ Deonarine A Chan DS. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA. (2013 ) 110:20212–7.

    Not in our library10.1073/pnas.1320318110

  90. 90.

    Li B Zeng Y Reeves PM Ran C Liu Q Qu X. AMD3100 augments the efficacy of mesothelin-targeted, immune-activating VIC-008 in mesothelioma by modulating intratumoral immunosuppression. Cancer Immunol Res. (2018 ) 6:539–51.

    Not in our library10.1158/2326-6066.cir-17-0530

  91. 91.

    Gravina GL Mancini A Marampon F Colapietro A Delle Monache S Sferra R. The brain-penetrating CXCR4 antagonist, PRX177561, increases the antitumor effects of bevacizumab and sunitinib in preclinical models of human glioblastoma. J Hematol Oncol. (2017 ) 10:5.

    Not in our library10.1186/s13045-016-0377-8

  92. 92.

    Massara M Bonavita O Savino B Caronni N Mollica Poeta V Sironi M. ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity. Nat Commun. (2018 ) 9:676.

    Not in our library10.1038/s41467-018-03080-8

  93. 93.

    Hansell CAH Fraser AR Hayes AJ Pingen M Burt CL Lee KM. The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis. J Immunol. (2018 ) 201:2510–9.

    Not in our library10.4049/jimmunol.1800131

  94. 94.

    Salazar N Carlson JC Huang K Zheng Y Oderup C Gross J. A chimeric antibody against ACKR3/CXCR7 in combination with TMZ activates immune responses and extends survival in mouse GBM models. Mol Ther. (2018 ) 26:1354–65.

    Not in our library10.1016/j.ymthe.2018.02.030

  95. 95.

    Oyajobi BO Franchin G Williams PJ Pulkrabek D Gupta A Munoz S. Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood. (2003 ) 102:311–9.

    Not in our library10.1182/blood-2002-12-3905

  96. 96.

    Horuk R. Chemokine receptor antagonists, overcoming developmental hurdles. Nat Rev Drug Discov. (2009 ) 8:23–33.

    Not in our library10.1038/nrd2734

  97. 97.

    Cullis J Siolas D Avanzi A Barui S Maitra A Bar-Sagi D. Macropinocytosis of Nab-paclitaxel drives macrophage activation in pancreatic cancer. Cancer Immunol Res. (2017 ) 5:182–90.

    Not in our library10.1158/2326-6066.cir-16-0125

  98. 98.

    Yao M Fang W Smart C Hu Q Huang S Alvarez N. CCR2 chemokine receptors enhance growth and cell cycle progression of breast cancer cells through SRC and PKC activation. Mol Cancer Res. (2018 ) 17:604–17.

    Not in our library10.1158/1541-7786.mcr-18-0750

  99. 99.

    Lu Y Cai Z Xiao G Liu Y Keller ET Yao Z. CCR2 expression correlates with prostate cancer progression. J Cell Biochem. (2007 ) 101:676–85.

    Not in our library10.1002/jcb.21220

  100. 100.

    Kalbasi A Komar C Tooker GM Liu M Lee JW Gladney WL. Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma. Clin Cancer Res. (2017 ) 23:137–48.

    Not in our library10.1158/1078-0432.ccr-16-0870

  101. 101.

    Allison SJ. Kidney cancer, CCR4, a new target for RCC. Nat Rev Nephrol. (2017 ) 13:192.

    Not in our library10.1038/nrneph.2017.14

  102. 102.

    Fuji S Shindo T Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma. Stem Cell Investig. (2016 ) 3:70

    Not in our library10.21037/sci.2016.09.13

  103. 103.

    González-Martín A Mira E Ma-es S. CCR5 in cancer immunotherapy, More than an “attractive” receptor for T cells. Oncoimmunology. (2012 ) 1:106–8.

    Not in our library10.4161/onci.1.1.17995

  104. 104.

    Velasco-Velazquez M Xolalpa W Pestell RG. The potential to target CCL5/CCR5 in breast cancer. Exp Opin Ther Targets. (2014 ) 18:1265–75.

    Not in our library10.1517/14728222.2014.949238

  105. 105.

    Hawila E Razon H Wildbaum G Blattner C Sapir Y Shaked Y CCR5 directs the mobilization of CD11b(+)Gr1(+)Ly6C(low) polymorphonuclear myeloid cells from the bone marrow to the blood to support tumor development. Cell Rep. (2017 ) 21:2212–22.

    Not in our library10.1016/j.celrep.2017.10.104

  106. 106.
    MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7 · 2012
    No notice
  107. 107.

    Cunningham H Kim E August K Vines C 948onovel single chain antibodies to inhibit Ccr7 mediated-entry of pediatric T-cell acute lymphoblastic leukemia into the Cns. Ann Oncol. (2014 ) 25(Suppl. 4):iv328

    Not in our library10.1093/annonc/mdu339.5

  108. 108.

    Yang L Jackson E Woerner BM Perry A Piwnica-Worms D Rubin JB. Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Cancer Res. (2007 ) 67:651–8.

    Not in our library10.1158/0008-5472.can-06-2762

  109. 109.

    Massara M Bonavita O Mantovani A Locati M Bonecchi R Atypical chemokine receptors in cancer, friends or foes? J Leukoc Biol. (2016 ) 99:927–33.

    Not in our library10.1189/jlb.3mr0915-431rr

  110. 110.

    Mantovani A Bonecchi R Locati M. Tuning inflammation and immunity by chemokine sequestration, decoys and more. Nat Rev Immunol. (2006 ) 6:907–18.

    Not in our library10.1038/nri1964

  111. 111.
    Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues · 2017
    No notice
  112. 112.

    Horuk R. The duffy antigen receptor for chemokines DARC/ACKR1. Front Immunol. (2015 ) 6:279.

    Not in our library10.3389/fimmu.2015.00279

  113. 113.

    Addison CL Belperio JA Burdick MD Strieter RM. Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis. BMC Cancer. (2004 ) 4:28.

    Not in our library10.1186/1471-2407-4-28

  114. 114.

    Shen H Schuster R Stringer KF Waltz SE Lentsch AB. The duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J. (2006 ) 20:59–64.

    Not in our library10.1096/fj.05-4764com

  115. 115.

    Khanna P Chung CY Neves RI Robertson GP Dong C. CD82/KAI expression prevents IL-8-mediated endothelial gap formation in late-stage melanomas. Oncogene. (2014 ) 33:2898–908.

    Not in our library10.1038/onc.2013.249

  116. 116.

    Wang J Ou ZL Hou YF Luo JM Shen ZZ Ding J. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene. (2006 ) 25:7201–11.

    Not in our library10.1038/sj.onc.1209703

  117. 117.

    Jenkins BD Hire R Howerth E Monteil M Martini R Davis MB Atypical chemokine receptor 1 (ACKR1/DARC) expressing tumors are associated with distinct recruitment of immune cells and increased pro-inflammatory chemokines. AACR. (2017 ) 77(Suppl.13):953

    Not in our library10.1158/1538-7445.am2017-953

  118. 118.

    Bonecchi R Locati M Galliera E Vulcano M Sironi M Fra AM. Differential recognition and scavenging of native and truncated macrophage-derived chemokine (macrophage-derived chemokine/CC chemokine ligand 22) by the D6 decoy receptor. J Immunol. (2004 ) 172:4972–6.

    Not in our library10.4049/jimmunol.172.8.4972

  119. 119.

    Nibbs RJ Kriehuber E Ponath PD Parent D Qin S Campbell JD. The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am J Pathol. (2001 ) 158:867–77.

    Not in our library10.1016/s0002-9440(10)64035-7

  120. 120.

    Lee KM Danuser R Stein JV Graham D Nibbs RJ Graham GJ. The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density. EMBO J. (2014 ) 33:2564–80.

    Not in our library10.15252/embj.201488887

  121. 121.

    Nibbs RJ Gilchrist DS King V Ferra A Forrow S Hunter KD. The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors. J Clin Invest. (2007 ) 117:1884–92.

    Not in our library10.1172/jci30068

  122. 122.

    Vetrano S Borroni EM Sarukhan A Savino B Bonecchi R Correale C. The lymphatic system controls intestinal inflammation and inflammation-associated Colon Cancer through the chemokine decoy receptor D6. Gut. (2010 ) 59:197–206.

    Not in our library10.1136/gut.2009.183772

  123. 123.

    Savino B Caronni N Anselmo A Pasqualini F Borroni EM Basso G. ERK-dependent downregulation of the atypical chemokine receptor D6 drives tumor aggressiveness in Kaposi sarcoma. Cancer Immunol Res. (2014 ) 2:679–89.

    Not in our library10.1158/2326-6066.cir-13-0202

  124. 124.

    Pacifico F Lepore A Mellone S Sanguigno L Federico G Greco A. The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid cancer. Genes Cancer. (2017 ) 8:577–88.

    Not in our library10.18632/genesandcancer.141

  125. 125.

    Bodduluri SR Mathis S Maturu P Krishnan E Satpathy SR Chilton PM Mast cell-dependent CD8+ T-cell recruitment mediates immune surveillance of intestinal tumors in Apc(Min/+) mice. Cancer Immunol Res. (2018 ) 6:332–47.

    Not in our library10.1158/2326-6066.cir-17-0424

  126. 126.

    Rajagopal S Kim J Ahn S Craig S Lam CM Gerard NP Beta-arrestin- but not G protein-mediated signaling by the “decoy” receptor CXCR7. Proc Natl Acad Sci USA. (2010 ) 107:628–32.

    Not in our library10.1073/pnas.0912852107

  127. 127.

    Scala S. Molecular pathways, targeting the CXCR4-CXCL12 axis–untapped potential in the tumor microenvironment. Clin Cancer Res. (2015 ) 21:4278–85.

    Not in our library10.1158/1078-0432.ccr-14-0914

  128. 128.

    Freitas C Desnoyer A Meuris F Bachelerie F Balabanian K Machelon V. The relevance of the chemokine receptor ACKR3/CXCR7 on CXCL12-mediated effects in cancers with a focus on virus-related cancers. Cytokine Growth Factor Rev. (2014 ) 25:307–16.

    Not in our library10.1016/j.cytogfr.2014.04.006

  129. 129.

    Sun X Cheng G Hao M Zheng J Zhou X Zhang J CXCL12/CXCR4 / CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev. (2010 ) 29:709–22.

    Not in our library10.1007/s10555-010-9256-x

  130. 130.

    Ieranò C Santagata S Napolitano M Guardia F Grimaldi A Antignani E. CXCR4 and CXCR7 transduce through mTOR in human renal cancer cells. Cell Death Dis. (2014 ) 5:e1310.

    Not in our library10.1038/cddis.2014.269

  131. 131.

    Wu YC Tang SJ Sun GH Sun KH. CXCR7 mediates TGFbeta1-promoted EMT and tumor-initiating features in lung cancer. Oncogene. (2016 ) 35:2123–32.

    Not in our library10.1038/onc.2015.274

  132. 132.

    Wang J Shiozawa Y Wang J Wang Y Jung Y Pienta KJ. The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem. (2008 ) 283:4283–94.

    Not in our library10.1074/jbc.m707465200

  133. 133.

    Maishi N Ohga N Hida Y Akiyama K Kitayama K Osawa T. CXCR7, a novel tumor endothelial marker in renal cell carcinoma. Pathol Int. (2012 ) 62:309–17.

    Not in our library10.1111/j.1440-1827.2012.02792.x

  134. 134.

    Comerford I Nibbs RJ Litchfield W Bunting M Harata-Lee Y Haylock-Jacobs S. The atypical chemokine receptor CCX-CKR scavenges homeostatic chemokines in circulation and tissues and suppresses Th17 responses. Blood. (2010 ) 116:4130–40.

    Not in our library10.1182/blood-2010-01-264390

  135. 135.

    Shi JY Yang LX Wang ZC Wang LY Zhou J Wang XY. CC chemokine receptor-like 1 functions as a tumour suppressor by impairing CCR7-related chemotaxis in hepatocellular carcinoma. J Pathol. (2015 ) 235:546–58.

    Not in our library10.1002/path.4450

  136. 136.

    Feng LY Ou ZL Wu FY Shen ZZ Shao ZM. Involvement of a novel chemokine decoy receptor CCX-CKR in breast cancer growth, metastasis and patient survival. Clin Cancer Res. (2009 ) 15:2962–70.

    Not in our library10.1158/1078-0432.ccr-08-2495

  137. 137.

    Zhu Y Tang W Liu Y Wang G Liang Z Cui L. CCX-CKR expression in colorectal cancer and patient survival. Int J Biol Markers. (2014 ) 29:e40–8.

    Not in our library10.5301/jbm.5000057

  138. 138.

    Harata-Lee Y Turvey ME Brazzatti JA Gregor CE Brown MP Smyth MJ. The atypical chemokine receptor CCX-CKR regulates metastasis of mammary carcinoma via an effect on EMT. Immunol Cell Biol. (2014 ) 92:815–24.

    Not in our library10.1038/icb.2014.58

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