Table 1.
Chemokines implicated in regulating immune responses in melanoma.
| Chemokines | Cellular sources | Regulation | Effect on innate immunity | Effect on adaptive immunity |
|---|---|---|---|---|
| CCL2 | Stromal/Immune cells (21) Melanoma (22) | Activation TNF (23) | Low levels of CCL2: recruitment of macrophages and enhanced angiogenesis and tumor formation (23) High levels of CCL2: infiltration of anti-tumor macrophages leading to tumor regression (23) | Expression correlated with increased tumor CD3+, CD8+ T cell infiltration (6, 24, 25), improved response to checkpoint inhibitors (25) and survival (24) |
| Lack of CCL2 or CCR2 reduced γδ T cell infiltration and increased tumor growth (26) | ||||
| CCL3-4 | Intratumoral myeloid derived suppressor cells (MDSCs) (8) | CCL3-4 in melanoma correlated with increased CD3+, CD8+ T cell infiltration (6, 24), and improved survival (24). Increased CCL4 in melanoma pre- and post- anti-CTLA4 (ipilimumab) treatment was associated with T cell infiltration and response to treatment (27) | ||
| CCL5 | Inhibition BECN1 autophagy gene (28) | NK cell recruitment into melanoma, associated with tumor regression (28) | CCL5 synergized with CXCL9 to recruit T cells into melanoma (29) | |
| CCL5, XCL1 | NK cells (5) | Inhibition PGE2 (5) | DC recruitment into melanoma and tumor growth inhibition (5) | |
| CCL20 | Tumor macrophages (30) | Activation TNF (30) | DC recruitment into melanoma and T cell-dependent inhibition of tumor growth (31) | |
| CCL21 | Melanoma cell lines MDA-MB-435S (32) and B16F10 (9) | Increased Treg infiltration and tumor growth (9) | ||
| CCL22 | Melanoma cell line B16F10 (33) | Overexpression of CCL22 in skin diverted Treg cells from lung metastasis leading to inhibition of metastatic growth in the lung (33) | ||
| CXCL1,2,5 | Tumor neutrophils (7) | Inhibition IFN-β (7) | Neutrophil recruitment into melanoma leading to angiogenesis and tumor growth (7). CXCL5 promoted neutrophil dependent tumor cell migration into lymphatic vessels (34). | |
| CCL5, CXCL9 - 11 | CCL5: Intratumoral MDSCs (8) CXCL9-10: CD103+ DC (5) CXCL9-11: Tumor endothelial cells (35) | CXCL9-10: Activation IFN (36) Inhibition Adenosine (37) | CCL5 and CXCL9-11 expression in melanoma correlated with increased CD8+ T cell infiltration (6), improved survival (24) and response to adoptive T cell therapy (38) CCL5, CXCL9-10 were associated with response to MAGE-A3 vaccine (39) CXCL9-11 recruited γδ T cells into melanoma (40) | |
| CXCL12 | Tumor macrophage (41) Tumor endothelium (42) | DC recruitment into melanoma, CD8+ T cell dependent tumor growth reduction (43) | CXCL12 recruited CTLs into melanoma (44) |