2026-05-19T01:29:20Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc 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 author 2024-08-30 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. 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 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