Table 1.
TME molecules and the effect on NK cells.
| TME molecule | Effect on NK cells | Cancer type | References |
|---|---|---|---|
| Hyaluronan | Impair access to tumor and ADCC | Breast and ovarian caner | (23) |
| Heparanase | Decrease recognition of target cells | Breast cancer | (24) |
| Galectin-1 | Impair cytotoxicity | Glioma | (25) |
| Galectin-3 | Galectin-3−/− mice have more effective cytotoxic CD27highCD11bhigh NK cells | Melanoma | (26) |
| Increase of galectin-3 impair NK cells cytotoxicity | Adenocarcinoma, cervix cancer | (27) | |
| Galectin-9 | Increase of NK cells infiltration | Melanoma | (28) |
| Downregulation of stimulatory genes (LTB, KLRF1, FCGR3A) and impair cytotoxicity against K562 cells | Leukemia | (29) | |
| Galectin-9 binds to TIM-3 leading to NK cells exhaustion | Gastrointestinal tumors | (30) | |
| Sialic acid | Low sialylation of tumor cells increases NK cell cytotoxicity | Melanoma | (31) |
| Siglec-7/9 | Membrane inhibitory receptor on NK cells that recognize sialic acid | Melanoma, basal cell carcinoma, squamous cell carcinoma, and cutaneous T cell lymphoma | (32) |
| MMP-9 | Cleaves MIC-A, MIC-B and ULBP-2 from tumor cells membrane avoiding killing by NK cells | Human gastric cancer, lung adenocarcinoma and osteosarcoma | (33–35) |
| ADAM-10/17 | Cleave MIC-B, ULBP-2 and B7-H6 from tumor cells membrane avoiding killing by NK cells | Human pancreatic adenocarcinoma, melanoma, cervical, breast, hepatocellular carcinomas and glioblastoma | (36–38) |