We are analyzing https://link.springer.com/article/10.1007/s00109-025-02557-6.

Title:
Tumor hypoxia shapes natural killer cell anticancer activities | Journal of Molecular Medicine
Description:
Tumor hypoxia, a hallmark of the tumor microenvironment (TME), profoundly impacts the antitumor functionality of immune cells, particularly natural killer (NK) cells, which play a critical role in cancer immunosurveillance and immunotherapy success. This review provides a comprehensive analysis of the mechanisms by which hypoxia impairs NK cell-mediated cytotoxicity and antitumor activities, emphasizing the molecular pathways and cellular adaptations that enable cancer cell to evade NK cell attack. Key factors that participate in this phenomenon include the stabilization of hypoxia-inducible factors, metabolic reprogramming, angiogenesis, cancer stemness, autophagy, and the secretion of immunosuppressive molecules. Moreover, hypoxia induces phenotypic and functional changes in both cancer and NK cells, promoting tumor progression and resistance to immunotherapy. Emerging strategies to counteract hypoxia-induced immunosuppression are being explored, including nanotechnology-based approaches, cytokine-mediated NK cell preconditioning, and vascular normalization techniques. These interventions highlight promising avenues for enhancing NK cell functionality and synergizing with existing cancer therapies. By addressing the immunosuppressive challenges of the hypoxic TME, in this review, we underscore the potential of innovative strategies to improve therapeutic outcomes in cancer treatment.
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Keywords {🔍}

pubmed, article, google, scholar, cas, cancer, cells, cell, central, tumor, immunol, hypoxia, natural, killer, httpsdoiorgs, res, immune, front, mol, microenvironment, nat, sci, immunotherapy, med, wang, hypoxiainduced, biol, cytotoxicity, httpsdoiorgfimmu, human, memorylike, role, hypoxiainducible, immunity, hypoxic, therapeutic, melanoma, rev, expression, int, targeting, factor, resistance, chen, huang, signaling, activation, cancers, cytotoxic, target,

Topics {✒️}

perk/eif2α/atf4/chop signaling pathway upregulating anxa3-hif-1α-vegf pathway targeting gef-h1/rhoa axis erbb2/her2-specific nk cells il-2/nkp46-activated nk cells tgf-β-mtor-hif-1 signaling hypoxia-inducible factor 1-alpha natural killer-mediated lysis hypoxia-inducible factor-1α flavio salazar-onfray myeloid-derived suppressor cells hypoxia-induced epithelial-mesenchymal transition hif-1α regulates function hypoxia-inducible factor induction enhance anti-tumor immunity hif-1α-dependent manner month download article/chapter hif-1α inhibition promotes enhanced nk-cell killing nk cell-mediated cytotoxicity hypoxia-induced vista promotes including nanotechnology-based approaches tumor-infiltrating nk cell cx43-gap junctions accumulate cytotoxic lymphocyte-derived tnf tumor-infiltrating immune cells death receptor–mediated cytotoxicity melanoma cell-derived exosomes immune checkpoint blockade hypoxia-mediated immune evasion optimizing oxygen-production kinetics targeting hypoxia-inducible factors tumor-infiltrating neutrophils protects pyroptosis‐based tumor immunotherapy nk cell–based immunotherapies hypoxia enhanced mdsc-mediated nk-cell lines stimulated tumor anti-angiogenic therapies foxo3a/ dusp6/erk axis hif1a-mediated immune escape natural killer cells counteract hypoxia-induced immunosuppression resists hypoxia-induced immunosuppression hypoxia-induced cell death mechanism involving tgf-β tissue-specific suppression hypoxia-induced cxcr4 expression ifn-dependent monocyte reprogramming decreased e-cadherin expression targeting cancer-derived adenosine

Questions {❓}

Barba I, Carrillo-Bosch L, Seoane J (2024) Targeting the Warburg effect in cancer: where do we stand?
Janji B, Chouaib S (2022) The promise of targeting hypoxia to improve cancer immunotherapy: mirage or reality?
Martínez-Lostao L, Anel A, Pardo J (2015) How do cytotoxic lymphocytes kill cancer cells?
Mazure NM, Pouysségur J (2010) Hypoxia-induced autophagy: cell death or cell survival?
Ortmann BM, Taylor CT, Rocha S (2024) Hypoxia research, where to now?
Stary V, Stary G (2020) NK cell-mediated recall responses: memory-like, adaptive, or antigen-specific?

Schema {🗺️}

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         description:Tumor hypoxia, a hallmark of the tumor microenvironment (TME), profoundly impacts the antitumor functionality of immune cells, particularly natural killer (NK) cells, which play a critical role in cancer immunosurveillance and immunotherapy success. This review provides a comprehensive analysis of the mechanisms by which hypoxia impairs NK cell-mediated cytotoxicity and antitumor activities, emphasizing the molecular pathways and cellular adaptations that enable cancer cell to evade NK cell attack. Key factors that participate in this phenomenon include the stabilization of hypoxia-inducible factors, metabolic reprogramming, angiogenesis, cancer stemness, autophagy, and the secretion of immunosuppressive molecules. Moreover, hypoxia induces phenotypic and functional changes in both cancer and NK cells, promoting tumor progression and resistance to immunotherapy. Emerging strategies to counteract hypoxia-induced immunosuppression are being explored, including nanotechnology-based approaches, cytokine-mediated NK cell preconditioning, and vascular normalization techniques. These interventions highlight promising avenues for enhancing NK cell functionality and synergizing with existing cancer therapies. By addressing the immunosuppressive challenges of the hypoxic TME, in this review, we underscore the potential of innovative strategies to improve therapeutic outcomes in cancer treatment.
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