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

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.

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Publication Details

Journal
Nature Communications
Published
2026-04-17
DOI
https://doi.org/10.1038/s41467-026-72036-0
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Lenka Kašíková, Munachiso Iheme Ndukwe, Radek Špíšek, Isabelle Cremer et al.
Nature Communications
Immune Cell Function and Interaction
article

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

Lenka Kašíková, Munachiso Iheme Ndukwe, Radek Špíšek, Isabelle Cremer, Šárka Vošáhlíková, Ann Vankerckhoven, Ján Laco, Jana Tománková, Irena Moserová, Tereza Láníčková, Francis Jacob, Linda Čapková, Ondřej Štěpánek, Veronika Niederlová, Lize Allonsius, Ema Zacharova, Marek Kovář, Daniela Glatzová, Lorenzo Galluzzi, D Cibula, Sandra Oršulić, Robert Lischke, Damya Laoui, Michal Hensler, Antoine Hanns, Christos Stekas, Artemis Angelidou, J Vachtenheim, Barbora TUNKOVÁ, Jitka Fucíkova, Lukas Rob, Jana Drozenova, Anna Bock, Thrinethra Shankar, Michal J. Halaska, Ales Ryska, Pavel Dundr, Barbora Cveckova
article en

Abstract

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.

Nature Communications
Fox Chase Cancer Center (US), Vrije Universiteit Brussel (BE), Inserm (FR), University of California, Los Angeles (US), University of Basel (CH), Czech Academy of Sciences (CZ), Université Paris Cité (FR), Charles University (CZ), University Hospital of Basel (CH), Sorbonne Université (FR), Centre de Recherche des Cordeliers (FR), University Hospital in Motol (CZ), Sotio (Czechia) (CZ), Czech Academy of Sciences, Institute of Microbiology (CZ), University Hospital Hradec Králové (CZ), Czech Academy of Sciences, Institute of Molecular Genetics (CZ), VIB-UGent Center for Inflammation Research (BE), University Hospital Kralovske Vinohrady (CZ), VA Greater Los Angeles Healthcare System (US), General University Hospital in Prague (CZ)
National Science Foundation, Leukemia and Lymphoma Society, Univerzita Karlova v Praze, Fakultní nemocnice Hradec Králové, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Grantová Agentura České Republiky, Akademie Věd České Republiky, Krebsliga Schweiz, National Institutes of Health, Stand Up To Cancer, European Regional Development Fund, Mikrobiologický Ústav, Akademie Věd České Republiky, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 25%
Immune Cell Function and Interaction
DOIOpen Access PDFOpenAlex
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