NKG2A inhibition promotes NK cell-CD8+ T cell interactions to improve anticancer immunity in ovarian carcinoma
Year: 2026
Type: article
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. The phenotypic and functional heterogeneity of Natural Killer (NK) cells between immunologically distinct tumor types has not been extensively investigated. Here, the authors combine multi-omic approaches, analysis of patient cohorts, and preclinical mouse models, comparing HGSOC to NSCLC as putative checkpoint-resistant and sensitive tumours. They observe an enrichment in NKG2A+ NK cells in HGSOC and propose that its inhibition boosts NK cell-CD8+ T cell interactions for improved cancer immunotherapy.
Source: Nature Communications
Authors: 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, 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
Institutions: Charles University, University Hospital in Motol, Sotio (Czechia), Czech Academy of Sciences, Czech Academy of Sciences, Institute of Molecular Genetics, University Hospital Kralovske Vinohrady, University Hospital Hradec Králové, General University Hospital in Prague, Czech Academy of Sciences, Institute of Microbiology, Vrije Universiteit Brussel, University of Basel, University Hospital of Basel, Inserm, Université Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, University of California, Los Angeles, VA Greater Los Angeles Healthcare System, Fox Chase Cancer Center, Fakultní nemocnice Motol a Homolka
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: 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
Awards: G1005326806, G1039539235, G1118322976, G1394090700, G1462752421, G2224250743, G2602218938, G2877016160, G3267687010, G3491845953, G3500543458, G3562932637, G3714817539, G3881116400, G390767198, G3988315726, G4095929368, G4256809665, G4490333144, G5350642298, Enhancing natural wastewater treatment systems: the role of particles in sunlight-mediated virus inactivation, G5946283803, G6734689452, G7185013638, G7290470516, G7931965296, G807766906, G85422383, Shedding light on the dark matter of tumor hybrid cells, G9000023995, G9000154262, Dynamics of Immune Response in Irradiated Rectal Cancer, Targeting the BCL2 immune checkpoint to enhance the immunostimulatory effects of radiation in breast cancer
OpenAlex ID: W7154726775