CK receptors, ligands, and their role in cancer
CK receptors | Ligands | Role | Cancer type | Immune cells involved | References |
---|---|---|---|---|---|
C-C motif CK receptor 1 (CCR1) | CCL3, CCL4, CCL5, CCL7, CCL8, CCL13, CCL14, CCL15, CCL16, CCL23 | Innate immunity and adaptive immunity | Breast cancer, lung cancer, prostate cancer, cervical cancer, hepatocellular carcinoma, multiple myeloma, T cell leukemia, osteosarcoma, colorectal cancer | Monocytes, macrophages, neutrophils, T helper 1 (Th1) cells, basophils, and DCs | [42] |
CCR2 | CCL2, CCL7, CCL8, CCL12, CCL13 | It helps monocytes move toward chemotactic signals and can be found on the surface of monocytes, basophils, activated memory T cells, and B cells | Breast cancer, pancreatic ductal, adenocarcinoma, glioma, lung cancer, prostate cancer, melanoma, multiple myeloma | TAMs, myeloid-derived suppressor cells (MDSCs), monocytes | [43, 44] |
CCR3 | CCL5, CCL7, CCL11, CCL13, CCL15, CCL24, CCL26, CCL28 | Expressed in several tissues’ keratinocytes, mast cells, Th2 cells, CD34+ hematopoietic progenitors, eosinophils, and basophils | Breast cancer, cervical cancer, renal cancer | Platelets | [45] |
CCR4 | CCR2, CCL3, CCL5, CCL7, CCL22 | CCR4 is preferentially expressed in Treg and Th2 cells. The expression can be transiently upregulated following T-cell receptor (TCR) and CD28 engagement | T cell leukemia, Hodgkin lymphoma, breast cancer, melanoma, hepatocellular carcinoma | Treg cells, monocytes, platelets | [46] |
CCR5 | CCL3, CCL4, CCL5, CCL8 | It is the major co-receptor associated with vulnerability to human immunodeficiency virus type 1 (HIV-1) infection. It is expressed by several cell types, including peripheral blood-derived DCs, CD34+ hematopoietic progenitor cells, and memory T cells | Breast cancer, cervical cancer, lung cancer, multiple myeloma, osteosarcoma, pancreatic cancer, prostate cancer | TAMs | [47, 48] |
CCR7 | CCL19, CCL21 | Expressed in lymphoid tissues and in B and T cells that have been activated. Controls the movement of memory T cells to irritated tissues and promotes the maturation of DCs | Breast cancer, gastric cancer, colorectal cancer, lung cancer, esophageal cancer, B cell leukemia | T cells, Th22 cells, T cells, Treg cells, DCs | [49] |
CCR8 | CCL1, CCL4, CCL17 | Immune surveillance in the skin, type 2 adaptive immunity, and thymopoiesis | Breast cancer | Th2 cells, Treg cells, skin tissue resident memory T (Trm) cells, γδ T cells, monocytes, and macrophages | [50] |
CCR10 | CCL27, CCL28 | Most often expressed by Th2 lymphocytes in the thymus | Leukemia, melanoma | Treg cells | [51] |
C-X-C motif CK receptor 3 (CXCR3) | CXCL9, CXCL10, CXCL11 | Mostly seen on T lymphocytes. It is quickly turned on in naive cells after they are activated, and it stays high in Th1 CD4+ T cells and effector CD8+ T cells | Pancreatic cancer, prostate cancer, breast cancer | Th1 cells, CD8+ central memory T (Tcm) and effector memory T (Tem) cells, natural killer (NK) cells, NKT cells, plasmacytoid DCs (pDCs), B cells. Treg cells, and T follicular helper (Tfh) cells | [52] |
CXCR4 | CXCL12 | Hematopoiesis, organogenesis, and bone marrow homing | Breast cancer, prostate cancer, gastric cancer, esophageal cancer, endothelial cells, ovarian cancer | MDSCs, TAMs, neutrophils | [53] |
CXCR5 | CXC13 | B cell and T cell trafficking in lymphoid tissue to the B cell zone or follicles | Lymphomas, pancreatic cancer, colon cancer, head and neck carcinomas | B cells, Tfh cells, T follicular regulatory (Tfr) cells, and CD8+ Tem cells | [54] |
CXCR6 | CXCL16 | Preferentially expressed on Th1 T cells. CXCR6 has been identified as a minor co-receptor for HIV-1 infection and in adaptive immunity | Breast cancer cells, gastric cancer cells, hepatocellular carcinoma cells, non-small cell lung cancer cells | Th1 cells, Th17 cells, γδ T cells, ILCs, NKT cells, NK cells, plasma cells, and endothelial cells | [55] |
C-X3-C motif CK receptor 1 (CX3CR1) | C-X3-C motif CK ligand 1 (CX3CL1) | Patrolling monocytes in innate immunity, microglial cell and NK cell migration, and type 1 adaptive immunity | Pancreatic cancer, prostate cancer, breast cancer | TAMs, resident monocytes, macrophages, Th1 cells, CD8+ Tem cells, NK cells | [56, 57] |
RS thanks Indian council of medical council research (ICMR), India; No. 2021-12946/CMB-BMS for senior research fellowship. The Figures were created with BioRender software (https://biorender.com/).
RS, PS: Writing—original draft, Writing—review & editing. PPM: Conceptualization, Supervision.
The authors declare that they have no conflicts of interest.
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This work was supported by IOE grant, No. R/Dev/D/IOE/Incentive/2021-22/32275 to Partha Pratim Manna by Banaras Hindu University (BHU). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2023.