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<p>Natural killer (NK) cells contribute to tumor immunosurveillance, yet their heterogeneity across cancer types remains incompletely understood. Transcriptomic, spatial, and functional assays reveal that non-small cell lung carcinoma (NSCLC) is enriched in NK cells that mediate clinically relevant effector functions, whereas high-grade serous ovarian carcinoma (HGSOC) contains dysfunctional NK cells that express co-inhibitory receptors including NKG2A. Analysis of HGSOC patient samples and syngeneic mouse models indicates a crosstalk between NK cells and CD8⁺ T cells critical for effective antitumor immunity. Depletion of either population leads to phenotypic impairment of the reciprocal one. Blocking NKG2A restores NK cell cytotoxicity and promotes CD8⁺ T cell responses, significantly improving the efficacy of PD-1 blockade in murine HGSOC models. Thus, NK cells and CD8⁺ T cells engage in a functional interplay of immunological relevance. Moreover, the NKG2A–HLA-E axis represents a clinically actionable immunological checkpoint in tumors with impaired NK cell functions.</p>

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NKG2A inhibition promotes NK cell-CD8+ T cell interactions to improve anticancer immunity in ovarian carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Tereza Lanickova,
  • Artemis Angelidou,
  • Michal Hensler,
  • Ann Vankerckhoven,
  • Veronika Niederlova,
  • Sarka Vosahlikova,
  • Lenka Kasikova,
  • Anna Bock,
  • Ema Zacharova,
  • Christos Stekas,
  • Barbora Tunkova,
  • Jana Tomankova,
  • Daniela Glatzova,
  • Irena Moserova,
  • Jana Drozenova,
  • Barbora Cveckova,
  • Thrinethra Shankar,
  • Jan Laco,
  • Ales Ryska,
  • Pavel Dundr,
  • Munachiso Iheme Ndukwe,
  • David Cibula,
  • Jiri Vachtenheim Jr.,
  • Robert Lischke,
  • Linda Capkova,
  • Marek Kovar,
  • Michal J. Halaska,
  • Lukas Rob,
  • Lize Allonsius,
  • Damya Laoui,
  • Antoine Hanns,
  • Isabelle Cremer,
  • Sandra Orsulic,
  • Ondrej Stepanek,
  • Francis Jacob,
  • Lorenzo Galluzzi,
  • Radek Spisek,
  • Jitka Fucikova

摘要

Natural killer (NK) cells contribute to tumor immunosurveillance, yet their heterogeneity across cancer types remains incompletely understood. Transcriptomic, spatial, and functional assays reveal that non-small cell lung carcinoma (NSCLC) is enriched in NK cells that mediate clinically relevant effector functions, whereas high-grade serous ovarian carcinoma (HGSOC) contains dysfunctional NK cells that express co-inhibitory receptors including NKG2A. Analysis of HGSOC patient samples and syngeneic mouse models indicates a crosstalk between NK cells and CD8⁺ T cells critical for effective antitumor immunity. Depletion of either population leads to phenotypic impairment of the reciprocal one. Blocking NKG2A restores NK cell cytotoxicity and promotes CD8⁺ T cell responses, significantly improving the efficacy of PD-1 blockade in murine HGSOC models. Thus, NK cells and CD8⁺ T cells engage in a functional interplay of immunological relevance. Moreover, the NKG2A–HLA-E axis represents a clinically actionable immunological checkpoint in tumors with impaired NK cell functions.