Natural killer (NK) cells are pivotal in the innate immune response against cancer and viral infections, with their presence in tumors correlating to better patient outcomes in various cancers.
Frontiers JournalsNov 27 2024 Natural killer cells are pivotal in the innate immune response against cancer and viral infections, with their presence in tumors correlating to better patient outcomes in various cancers. However, NK cells in the tumor microenvironment often become functionally exhausted, characterized by decreased numbers and impaired functions due to imbalances in immune regulatory signals.
Intracellular checkpoint molecules like BIM, which mediates apoptosis in NK cells, can be targeted to enhance antitumor responses. The absence of BIM in NK cells has been shown to increase their resistance to apoptosis and accumulate in later stages of maturation, potentially enhancing their antitumor capabilities. Similarly, Cbl-b, an E3 ubiquitin protein ligase, negatively regulates NK cell cytolytic activity, and its inhibition can improve NK cell-mediated control of tumor metastasis.
TIPE2, a negative regulator of IL-15 signaling, is upregulated in various conditions and suppresses downstream AKT and Ral activation. The absence of TIPE2 in NK cells results in enhanced functional maturation, cytotoxicity, and IFN-γ production, indicating its potential as a checkpoint for NK cell immunotherapy. HIF-1α, a transcription factor involved in cellular responses to hypoxia, negatively regulates IL-18-driven NF-κB signaling and antitumor activity of tumor-infiltrating NK cells.
Cancer Immunotherapy Cell Immunotherapy Intracellular Apoptosis Cytotoxicity Efficacy Exhaustion Gene Immune Response Immunity Metabolism Proliferation Tumor
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