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Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics

dc.rights.licenseopenen_US
dc.contributor.authorCOUSIN, Sophie
dc.contributor.authorGUEGAN, Jean-Philippe
dc.contributor.authorSHITARA, Kohei
dc.contributor.authorPALMIERI, Lola Jade
dc.contributor.authorMETGES, Jean Philippe
dc.contributor.authorPERNOT, Simon
dc.contributor.authorFUKUOKA, Shota
dc.contributor.authorKOYAMA, Shohei
dc.contributor.authorNISHIKAWA, Hiroyoshi
hal.structure.identifierCentre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux
hal.structure.identifierInstitut de Santé Publique, d'Epidémiologie et de Développement [ISPED]
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierDépartement de recherche clinique et d'information médicale
hal.structure.identifierCIC Bordeaux
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBELLERA, Carine
dc.contributor.authorADENIS, Antoine
dc.contributor.authorGOMEZ-ROCA, Carlos A
dc.contributor.authorCASSIER, Philippe Alexandre
dc.contributor.authorHOLLEBECQUE, Antoine
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCANTAREL, Coralie
dc.contributor.authorKIND, Michele
dc.contributor.authorSOUBEYRAN, Isabelle
dc.contributor.authorVANHERSECKE, Lucile
dc.contributor.authorBESSEDE, Alban
dc.contributor.authorITALIANO, Antoine
dc.date.accessioned2024-10-17T13:43:44Z
dc.date.available2024-10-17T13:43:44Z
dc.date.issued2024-09-13
dc.identifier.issn1476-4598en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202561
dc.description.abstractEnAnti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. This therapeutic regimen resulted in deep and durable responses in 19% of patients, with the median duration of response not yet reached. Notwithstanding, a significant proportion of AGC patients exhibited no therapeutic advantage, prompting investigations into mechanisms of inherent resistance. Comprehensive biomarker profiling elucidated that non-responders predominantly exhibited an augmented presence of M2 macrophages within the tumor microenvironment and a marked overexpression of S100A10 by neoplastic cells, a protein previously implicated in macrophage chemotaxis. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enIdentification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics
dc.title.alternativeMol Canceren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1186/s12943-024-02092-xen_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed39272096en_US
bordeaux.journalMolecular Canceren_US
bordeaux.page197en_US
bordeaux.volume23en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamEPICENE_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDBayer Foundationen_US
hal.identifierhal-04741879
hal.version1
hal.date.transferred2024-10-17T13:43:47Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Cancer&rft.date=2024-09-13&rft.volume=23&rft.issue=1&rft.spage=197&rft.epage=197&rft.eissn=1476-4598&rft.issn=1476-4598&rft.au=COUSIN,%20Sophie&GUEGAN,%20Jean-Philippe&SHITARA,%20Kohei&PALMIERI,%20Lola%20Jade&METGES,%20Jean%20Philippe&rft.genre=article


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