Published 4 issues per year
ISSN Print: 2694-4642
ISSN Online: 2694-4650
Indexed in
Nitric Oxide-Mediated Regulation of Cancer Immune Escape
ABSTRACT
There is now evidence that nitric oxide (NO) regulates hypoxia-induced malignant phenotypes such as invasiveness, metastatic ability, and drug resistance in tumor cells. Recent studies have also revealed that the ability of tumor cells to avoid destruction by innate immune effector mechanisms (immune escape) is stimulated by hypoxia through a mechanism that appears to involve inhibition of NO signaling. Specifically, it was shown that NO activity blocks the hypoxia-induced resistance of prostate cancer cells to the lytic activity of peripheral blood lymphocytes by preventing the shedding of major histocompatibility complex class I chain-related (MIC) molecules from the tumor cell membrane. MIC plays an important role in tumor immune surveillance through its interaction with the NKG2D receptor on natural killer and cytotoxic T cells. These findings suggest that the hypoxic tumor microenviron-ment contributes to impaired immune surveillance, and that activation of NO signaling is of potential use in cancer immunotherapy.