{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:59:22Z","timestamp":1790125162647,"version":"4.0.1"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"10","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:p>\n                    Glucocorticoids (GCs) are potent immunosuppressive agents that compromise anticancer immune responses, yet the molecular mediators of this effect remain incompletely understood. Here, we identify the acyl-CoA-binding protein\/diazepam-binding inhibitor (ACBP\/DBI) as a critical effector of the GC-induced suppression of tumor immunosurveillance and immunotherapy efficacy. Using orthotopic murine models of breast cancer, non\u2013small cell lung cancer, and cutaneous fibrosarcoma, we show that corticosterone (CORT) accelerates tumor progression and abrogates therapeutic responses to immunogenic chemotherapy and PD-1 blockade. Genetic ablation or monoclonal antibody (mAb)-mediated neutralization of ACBP\/DBI prevents immunosuppression by CORT, restoring both natural and therapy-enhanced antitumor immunity in a T cell\u2013dependent manner. Mechanistically, CORT induces\n                    <jats:italic toggle=\"yes\">Tsc22d3<\/jats:italic>\n                    expression in dendritic cells, impairs type I interferon signaling, and reduces antigen presentation capacity, which all can be reversed by ACBP\/DBI neutralization. The immunosuppressive activity of GCs and the immunostimulatory function of anti-ACBP\/DBI mAb converge on\n                    <jats:italic toggle=\"yes\">Tsc22d3<\/jats:italic>\n                    expression in myeloid cells, as shown by loss-of-function experiments in myeloid-specific\n                    <jats:italic toggle=\"yes\">Tsc22d3<\/jats:italic>\n                    -deficient mice. These findings reveal ACBP\/DBI as a central mediator of GC-induced immune evasion and suggest its neutralization as a therapeutic strategy to restore anticancer immunity during endogenous or iatrogenic GC exposure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2518983123","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:40:32Z","timestamp":1772649632000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Neutralization of acyl-CoA-binding protein attenuates glucocorticoid-mediated suppression of cancer immunosurveillance"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5500-7806","authenticated-orcid":false,"given":"Hui","family":"Pan","sequence":"first","affiliation":[{"name":"Team Metabolism, Cancer & Immunity, Centre de Recherche des Cordeliers, Equipe labellis\u00e9e par la Ligue contre le cancer, Inserm U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9","place":["Paris, France"]},{"name":"Metabolomics and Cell Biology Platforms, Unit\u00e9 Mixte de Service Analyse Mol\u00e9culaire, Mod\u00e9lisation et Imagerie de la Maladie Canc\u00e9reuse, Gustave Roussy","place":["Villejuif, France"]},{"name":"Department of Hematology\/Institute of Hematology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Shen","sequence":"additional","affiliation":[{"name":"Team Metabolism, Cancer & Immunity, Centre de Recherche des Cordeliers, Equipe labellis\u00e9e par la Ligue contre le cancer, Inserm U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9","place":["Paris, France"]},{"name":"Metabolomics and Cell Biology Platforms, Unit\u00e9 Mixte de Service Analyse Mol\u00e9culaire, Mod\u00e9lisation et Imagerie de la Maladie Canc\u00e9reuse, Gustave Roussy","place":["Villejuif, France"]},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris-Saclay","place":["Le Kremlin Bic\u00eatre, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Team Metabolism, Cancer & Immunity, Centre de Recherche des Cordeliers, Equipe labellis\u00e9e par la Ligue contre le cancer, Inserm U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9","place":["Paris, France"]},{"name":"Metabolomics and Cell Biology Platforms, Unit\u00e9 Mixte de Service Analyse Mol\u00e9culaire, Mod\u00e9lisation et Imagerie de la Maladie Canc\u00e9reuse, Gustave Roussy","place":["Villejuif, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-9222","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Team Metabolism, Cancer & Immunity, Centre de Recherche des Cordeliers, Equipe 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