Table 2.
Expression of chemokine and chemokine receptors by immune cells associated with melanoma control or progression.
| Chemokine receptor | Immune cell expression | Roles in melanoma development/progression | Cohort details | Statistical analyses | References |
|---|---|---|---|---|---|
| CCR2 | Tumor macrophages and MDSC | Neutralization decreased tumor macrophage accumulations associated with a reduction of tumor angiogenesis and tumor growth | Preclinical studies | (98, 99) | |
| CCR4 | Blood and tumor Tregs | Depletion enhanced anti tumor immune responses. Controversial using the spontaneous Ret melanoma model. | In vitro and preclinical studies | (96, 97, 100) | |
| CCR5 | Blood and tumor Tregs and MDSC | CCR5Δ32 polymorphism in patients receiving immunotherapy associated with decreased survival Immunosuppression -Neutralization resulted in increased survival of tumor bearing mice | 139 stage IV patients Preclinical studies | Log-rank test and Cox regression– P = 0.002 | (101–104) |
| CCR6 | Blood and tumor pDC—Blood CD8+ T cells | Higher expression in melanoma patients—circulating effector CCR6+CD8+ T cells and CCL20 expressed by tumor-associated macrophages conveyed a dismal prognosis | 40 primary melanomas−57 stage III-IV patients | Log rank test and Cox regression | (38, 105, 106) |
| CCR9 | Blood CD8+ TNaive | Associated with increased overall survival | 57 stage III-IV patients | Log-rank test and Cox regression–P = 0.0036 (Stage-adjusted) | (106) |
| CCR10 | Blood CD4+ TEM | Associated with worse survival | 57 stage III-IV patients | Log-rank test and Cox regression–P = 0.0189 (Stage-adjusted) | (106) |
| CXCR2 | Tumor MDSC and neutrophils | Accumulation of tumor CXCR2+ MDSC and neutrophils. CXCR2 neutralization reduced tumor growth | Preclinical studies | (107, 108) | |
| CXCR3 | Blood and tumor CD4+ and CD8+ TEM | Critical in intratumoral T cell trafficking—Associated with clinical benefit | Preclinical studies–Stage III-IV patients | Log-rank test, χ2 and Cox regression | (87, 106, 109, 110) |
| CXCR4 | Blood CD45RA+CD4+ T cells | Associated with prolonged disease free survival | 195 stage I-III patients | Log-rank test and Cox regression–P = 0.0091 | (111) |
TEM: Effector memory T cells.