Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma

Article Article scientifique Article Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma eng 2026-07-31 author Pedard Martin 0000-0003-1258-7825 422242 Département de médecine (DEMED) author Castillo Cantero Luis 983983 Département de médecine (DEMED) author Ghasemi Ali 422689 Département de médecine (DEMED) author Marinari Eliana 841772 Département de médecine (DEMED) author Mollica Caterina author Davanture Suzel 982947 Département de médecine (DEMED) author Pernot Julie 443810 Département de médecine (DEMED) author Widmer-Schnuriger Valérie 39000 Département de médecine (DEMED) author Merkler Doron 0000-0002-0247-2007 735735 Département de pathologie et immunologie (PATIM) author Egervari Kristof Levente 0000-0001-6763-9069 761273 author Schaller Karl Lothard 658606 Département des neurosciences cliniques (OTONO) author Bijlenga Philippe Alexandre Pierre 0000-0002-3586-2757 104899 Département des neurosciences cliniques (OTONO) author Bartoli Andréa 840772 Département des neurosciences cliniques (OTONO) author Momjian Shahan Marc 84022 Département des neurosciences cliniques (OTONO) author Pittet Mikaël 0000-0002-2060-4691 917678 Département de pathologie et immunologie (PATIM) author Dutoit Vallotton Valérie 0000-0002-3469-4237 668630 Département de médecine (DEMED) author Migliorini Denis 0000-0003-0151-3222 838158 Département de médecine (DEMED) 10.1038/s41467-026-76206-y 2041-1723 https://www.nature.com/articles/s41467-026-76206-y Glioblastoma (GBM) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that constrains the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Here, we show that surgical resection in both male mice and human GBM ex vivo induces a rapid and sustained remodeling of the TME, marked by upregulation of TREM2 in myeloid cells followed by emergence of T cell exhaustion-like phenotypes. In male mice, targeting TREM2 reshapes the perioperative TME and potentiates tumor antigen-specific CAR-T cell responses, improving intratumoral persistence, proliferation, and effector differentiation, and resulting in enhanced survival. In parallel, we identify the timing of CAR-T cell administration as a critical determinant of therapeutic outcome, with neoadjuvant outperforming adjuvant treatment by preserving CAR-T cell effector function in mice. These findings establish perioperative myeloid cell remodeling and treatment timing as key determinants of CAR-T cell efficacy in GBM. Dewey 610 Dewey 616.8 Dewey 616.07 Dewey 616 4f7589ed-e44d-4850-a4d8-b0c1eccdfe48 Centre de recherche translationnelle en onco-hématologie 209 61 Département des neurosciences cliniques 226 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 1310 Tumeurs cérébrales 1016 565 La Sclérose en plaques 908 513 Groupe Schaller Karl Lothard (neurochirurgie) 851 1336 Comprendre et manipuler le système immunitaire pour lutter contre le cancer 1024 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM8703639 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM8703640 https://github.com/pedarmar-git/TREM2_GFP_analysis https://zenodo.org/records/21097173 Nature communications 96b50888-4421-40f5-b440-2aff4933f2cf Article (Accepted version) Public Pedard_Nature_Comm_2026.pdf 10216545 application/pdf CC BY-4.0 002c5df18cf6ef8edc67963c37412ffe45a4947669ff81acc3545faa4fe462aa c0faf0d5-3886-4392-a462-0107664b4d3f Supplemental data Public 41467_2026_76206_MOESM1_ESM.pdf 6847326 application/pdf e76b1d70755a3c5245abb53d11031b81c3ae5c7eefc63642f7eeb0c4ed472368 d6f33bc6-813d-4a50-a835-ca8145fb864f Supplemental data Public 41467_2026_76206_MOESM2_ESM.pdf 118955 application/pdf 01e8a3441d8b70de6712962adc77f254dfd130abea16967c59f12072dec325b4 1456b573-abe9-44fa-ae0b-6e99eb6d4a41 Supplemental data Public 41467_2026_76206_MOESM3_ESM.pdf 9064163 application/pdf 7ef82690409cd0c5184647218e3e9b8d9d37234fbf14092bd0d7f450612c1177 aa5c5f59-6261-4221-aa5f-f8d36153017f Supplemental data Public 41467_2026_76206_MOESM4_ESM.xlsx 1738084 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 3458ebfd93803a1c1a986ef747e7c8c75988c92536a61af4ad5460a3005bb7cf openAccess Faculté de médecine / Centre de recherche translationnelle en onco-hématologie Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine

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Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma	Nature communications			2026	32	21

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Pernot, Julie