Natural Killer Cell Suppression in the Tumour Microenvironment: Mechanisms and Therapeutic Opportunities
DOI:
https://doi.org/10.58445/rars.2811Keywords:
Natural killer (NK) cells, Tumor microenvironment (TME)Abstract
Natural killer (NK) cells are a critical component of the innate immune system, responsible for detecting and eliminating virally infected and malignant cells. However, NK cell function is often suppressed in the tumour microenvironment (TME), allowing tumour cells to evade immune surveillance. This review examines the primary mechanisms by which the TME suppresses NK cell activity, including the impact of immunosuppressive molecules such as adenosine, hypoxia, lactate, prostaglandin E2 (PGE2), and transforming growth factor-beta (TGF-β). These molecules collectively inhibit NK cell metabolism, suppress cytokine production, and diminish cytotoxic activity, ultimately promoting tumour progression. Additionally, we discuss the role of other immunosuppressive cell populations, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2-like tumour-associated macrophages (TAMs), which further contribute to immune evasion. A deeper understanding of these suppressive pathways is essential for developing novel immunotherapeutic strategies aimed at restoring NK cell function in cancer. Future efforts should focus on disrupting these inhibitory signals through approaches such as metabolic reprogramming, immune checkpoint blockade, and combination therapies to reinvigorate NK cell-mediated tumour elimination.
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