The Emerging Role of CXC Chemokines And Their Receptors in Cancer

Vinader, V.; Afarinkia, K.

doi:10.4155/fmc.12.48

Cited by 33 publications

(24 citation statements)

References 212 publications

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“…CXCR2 expression in endothelial cells is activated by ELR + CXC chemokines and promotes tumor growth [23]. CXCR2 was also documented to be correlated with intrahepatic metastasis, portal cancer embolus and TNM staging of liver cancer patients [20,24-27], although the role of CXCR2 in tumor cells is debated.…”

Section: Discussionmentioning

confidence: 99%

Roles of CXCL5 on migration and invasion of liver cancer cells

Huang

Yang

et al. 2014

J Transl Med

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Inflammatory factors play a vital role in the progression of liver cancer, although exact factors and related mechanisms still remain unclear. The present study aimed at screening inflammatory factors related to liver cancer metastasis and investigating the potential mechanism by which cancer cells are recruited. We screened and validated inflammatory factors by microarray and RT-PCR. Small interfering RNA (siRNA) and recombinant protein were used to assess CXCL5 effects on the movement of liver cancer cells (LCCs). Our screening microarray demonstrated over-expression of CXCL5 in LCCs with high metastatic potentials. CXCL5 increased LCCs migration and invasion, probably through autocrine and paracrine mechanisms. CXCL5-CXCR2 and ERK1/2 pathways could play critical roles in the regulation of LCCs migration. Our data indicates that LCCs per se may act as the producer and receptor of CXCL5 responsible for liver cancer migration and invasion.

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Section: Discussionmentioning

confidence: 99%

Roles of CXCL5 on migration and invasion of liver cancer cells

Huang

Yang

et al. 2014

J Transl Med

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“…The chemokine landscape of the tumor microenvironment may differ significantly among tumors, and can affect immune cell composition, tumor growth and metastasis (17). Since leukocyte infiltration into tumors is controlled by chemokine gradients in the tumor microenvironment and cognate chemokine receptors expressed on immune cells (13, 18–20), decreased expression of appropriate chemokines can contribute to a lack of effector T cell infiltration and resistance to immunotherapy (21). Thus, successful immunotherapy should achieve an optimal match between the chemokine landscape of targeted tumors and the chemokine receptor repertoire expressed by the elicited effector T cells.…”

Section: Introductionmentioning

confidence: 99%

The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28–Costimulated T Cells Prepared for Adoptive Therapy

Zsiros

Duttagupta

Dangaj

et al. 2015

Clinical Cancer Research

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Purpose: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy.Experimental Design: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer. Results:The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4, and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12, and CXCL16 are expressed quasi-universally, including in tumors lacking tumorinfiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed Tcells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer.Conclusions: DC-primed tumor-specific T cells are armed with the appropriate receptors to migrate toward universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating toward these chemokines. Clin Cancer Res; 21(12); 2840-50. Ó2015 AACR.

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“…The entirety of the chemokine receptor and ligand family has been implicated in various aspects of immune biology that may have important effects in cancer 139,141,142 . A number of these drug targets have been considered for cancer intervention based largely on their role in trafficking, retention and activation of immune infiltrate and, in some cases, preclinical and even clinical cancer investigations have been initiated 139 (see Supplementary information S2 (table)).…”

Section: Chemokinesmentioning

confidence: 99%

Big opportunities for small molecules in immuno-oncology

Adams

Smothers

Srinivasan

et al. 2015

Nat Rev Drug Discov

383

303

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The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer immunotherapies with durable clinical effects. Most of these breakthrough medicines are monoclonal antibodies that block protein-protein interactions between T cell checkpoint receptors and their cognate ligands. In addition, genetically engineered autologous T cell therapies have also recently demonstrated significant clinical responses in haematological cancers. Conspicuously missing from this class of therapies are traditional small-molecule drugs, which have previously served as the backbone of targeted cancer therapies. Modulating the immune system through a small-molecule approach offers several unique advantages that are complementary to, and potentially synergistic with, biologic modalities. This Review highlights immuno-oncology pathways and mechanisms that can be best or solely targeted by small-molecule medicines. Agents aimed at these mechanisms--modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration--are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.

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The Emerging Role of CXC Chemokines And Their Receptors in Cancer

Cited by 33 publications

References 212 publications

Roles of CXCL5 on migration and invasion of liver cancer cells

Roles of CXCL5 on migration and invasion of liver cancer cells

The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28–Costimulated T Cells Prepared for Adoptive Therapy

Big opportunities for small molecules in immuno-oncology

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