2026-05-19T01:29:21Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/250972025-12-18T12:59:18Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16938col_20.500.12105_19617
Repisalud
author
Dios Huerta, Olaya de
author
Ramírez-González, María A
author
Gómez-Soria, Irene
author
Segura-Collar, Berta
author
Manosalva, Juliana
author
Megías, Diego
author
de Andrea, Carlos E
author
Fernández-Rubio, Leticia
author
Hernández-Laín, Aurelio
author
Sepúlveda-Sánchez, Juan Manuel
author
Rodriguez-Ruiz, Maria E
author
Pérez-Núñez, Ángel
author
Wainwright, Derek A
author
Gargini, Ricardo
author
Sánchez-Gómez, Pilar
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
National Institutes of Health (Estados Unidos)
funder
Cancer Research UK (Reino Unido)
funder
American Cancer Society
funder
Asociación Española Contra el Cáncer
funder
Brain Tumor Association (ABTA)
2024-10-14T10:51:10Z
2024-10-14T10:51:10Z
2024-08-30
J Immunother Cancer. 2024 Aug 30;12(8):e009210.
10.1136/jitc-2024-009210
2051-1426
Journal for immunotherapy of cancer
39214651
https://hdl.handle.net/20.500.12105/25097
Background: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment. Methods: We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response. Results: We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association. Conclusions: This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials.
eng
Central Nervous System Cancer
Immune Checkpoint Inhibitor
Macrophage
NK Cell Lectin-Like Receptor Subfamily K
Tumor microenvironment - TME
NKG2C/ KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma
research article
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