Table 1 HIF signal pathways in tumor immune escape
From: Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape
Targets/effectors | Model | Mechanisms of tumor immune escape | Refs. |
|---|---|---|---|
CD47 | Human breast cell lines | HIF1 regulates CD47 expression to promote evasion of phagocytosis | [93] |
VEGF | Human primary breast cells | HIF1A-induced VEGF correlates with PD-L1 expression | [91] |
PD-L1 | Human prostatic carcinoma cells Mouse B16-F10 melanoma | HIF1A upregulates PD-L1 expression in tumor cells causing T-cell apoptosis | [47] |
VSIR | BALB/c mice CT26 colon carcinoma cell line | Hypoxia-induced VISTA, by HIF1A binding to the VISTA promoter, suppresses T-cell activity | [27] |
MICs | The PANC-1 cell line Human pancreatic carcinoma cells | Hypoxia-induced MICs are shed from the tumors membrane to evade KLRK1-mediated immune surveillance | [101] |
CCL28 | Human haptic cell lines Hepatic cell lines Mouse hepatic cancer cells | HIF1A-dependently upregulates hypoxia-induced CCL28 to activate Tregs proliferation | [103] |
IL-23 | Human ccRCC tumor cells | Tumor cells induce tumor-infiltrating macrophages to secrete IL-23 by activating HIF1A, thereby inhibiting the killing capability of the cytotoxic lymphocytes | [28] |
miR224 | Human prostate cancer tissues | HIF1A upregulates miR-224 expression to inhibit the NK cells function by NCR1/NKp46 signaling | [105] |
GAL3ST1 | 786-O, RCC4, HEK293A, HEK293T, NK-92 cells, primary kidney tissues | HIF1A and HIF2A upregulate the GAL3ST1 levels as VHL loss or hypoxia, further GAL3ST1 regulates sulfatide expression to escape the NK-mediated cytotoxicity | [106] |
SCF | Human ccRCC tumor cells | HIF2A induces the SCF secretion thereby reducing immunosurveillance and impairing anti-tumor immunity | [29] |