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Abstract 2578: High regulatory T cells infiltrate within tertiary lymphoid structure restricts response to immune checkpoint blockers in sarcomas

dc.rights.licenseopenen_US
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorPEYRAUD, Florent
hal.structure.identifierExplicyte Immuno-Oncology [Bordeaux]
dc.contributor.authorGUEGAN, Jean-Philippe
hal.structure.identifierInstitut universitaire de France [IUF]
hal.structure.identifierLexiques, Textes, Discours, Dictionnaire - Centre Jean Pruvost [LT2D]
dc.contributor.authorREY, Christophe
hal.structure.identifierCIC Bordeaux
dc.contributor.authorPULIDO, Marina
hal.structure.identifierInstitut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO]
dc.contributor.authorBOMPAS, Emmanuelle
hal.structure.identifierInstitut Curie [Paris]
dc.contributor.authorPIPERNO-NEUMANN, Sophie
hal.structure.identifierInstitut Claudius Regaud [ICR]
dc.contributor.authorCHEVREAU, Christine
hal.structure.identifierUniversité Lille Nord de France (COMUE)
hal.structure.identifierCentre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
hal.structure.identifierEvaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
dc.contributor.authorPENEL, Nicolas
hal.structure.identifierCentre de Recherche en Cancérologie de Marseille [CRCM]
dc.contributor.authorBERTUCCI, François
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorTOULMONDE, Maud
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBELLERA, Carine
hal.structure.identifierCentre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
dc.contributor.authorSAUTÈS-FRIDMAN, Catherine
hal.structure.identifierCentre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
dc.contributor.authorBOUGOÜIN, Antoine
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCANTAREL, Coralie
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorKIND, Michèle
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorSPALATO-CERUSO, Mariella
hal.structure.identifierInstitut de Recherche sur le Cancer et le Vieillissement [IRCAN]
dc.contributor.authorDADONE-MONTAUDIE, Bérengère
hal.structure.identifierCentre Léon Bérard [Lyon]
hal.structure.identifierUniversité Claude Bernard Lyon 1 [UCBL]
hal.structure.identifierUNICANCER
dc.contributor.authorBLAY, Jean-Yves
hal.structure.identifierCentre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
dc.contributor.authorFRIDMAN, Wolf Herman
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorLOARER, François Le
hal.structure.identifierImmuSmol
dc.contributor.authorBESSEDE, Alban
dc.contributor.authorITALIANO, Antoine
dc.date.accessioned2024-09-18T07:48:15Z
dc.date.available2024-09-18T07:48:15Z
dc.date.created2022
dc.date.conference2022-04-08
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201639
dc.description.abstractEnAbstract Background: While composition of the tumor microenvironment (TME) is a prerequisite for an effective antitumor immunity, infiltration of organized B- and T-cells aggregates called tertiary lymphoid structures (TLS) has been recently demonstrated to predict response to immune checkpoint blockers (ICB) in sarcomas. However, only a minority of patient derive benefit, suggesting the implication of additional key determinants of ICB-mediated response in TLS-positive sarcomas, such as TLS composition. Using high-throughput spatial transcriptomics and multiplex immunofluorescence (IHF), we aimed at investigating the association between TLS composition and clinical outcome to ICB. Methods: In an exploratory cohort, we spatially profiled the expression of more than 18000-protein encoding genes from responders (R) and non-responders (NR) using Nanostring’s GeoMx Digital Spatial Profiler (DSP) Whole Transcriptome Atlas (WTA) assay. A first set of regions of interest (ROI) was selected in the TLS and further segmented in “B-cells” vs “no B-cells” areas according to CD20+ staining; a second set of ROI was selected in the tumor tissue and further segmented into “tumor” vs “stroma” areas according to CD45+ staining. Deconvolution of data was performed using SpatialDecon algorithm to estimate cell population within TLS. We then evaluated the association between immune cell composition and response to ICB in each segment. In a validation cohort, we performed multiplexed-IHF assay enabling detection of T cells (CD8/GzmA/CD4/FoxP3/CD56) and B cells. These panel was applied to whole sections baseline sarcoma samples. We investigated the association between immune cell composition and clinical benefit in term of progression-free survival (PFS) and overall survival (OS). Results: Six patients were selected for the exploratory cohort, including 3 R and 3 NR. Among the top immune cell infiltrate within TLS segment, NR demonstrated higher Treg infiltrate versus R in “no B-cells” compartment (3.4% vs 2.0%, respectively; p=0.010), whereas no association was observed between Treg infiltration and response to ICB in both stromal (p=0.67) or tumor cells (p=0.36) compartments from tumor area. In the validation cohort (N=16), we observed that Treg density within TLS was higher in NR versus R (p=0.0059). Patients with Treg-enriched TLS had shorter PFS (2.6 vs 11.1 months, p=0.042) and OS (9.0 vs 18.3 months, p=0.12) compared to those with Treg-low TLS infiltration. Concordantly, the CTLA-4 key Treg regulator gene was upregulated in the TLS regions from NR. Conclusions: Altogether, our findings suggest that the presence of Treg within TLS may exert a negative influence on the capacity of TLS to generate an effective antitumor immune response in sarcoma patients treated with ICB, providing new insights in understanding role of TLS in antitumor immunotherapy. Citation Format: Florent Peyraud, Jean-Philippe Guegan, Christophe Rey, Marina Pulido, Emmanuelle Bompas, Sophie Piperno-Neumann, Christine Chevreau, Nicolas Penel, François Bertucci, Maud Toulmonde, Carine Bellera, Catherine Sautès-Fridman, Antoine Bougoüin, Coralie Cantarel, Michèle Kind, Mariella Spalato-Ceruso, Bérengère Dadone-Montaudie, Jean-Yves Blay, Wolf Herman Fridman, François Le Loarer, Alban Bessede, Antoine Italiano. High regulatory T cells infiltrate within tertiary lymphoid structure restricts response to immune checkpoint blockers in sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2578.
dc.language.isoENen_US
dc.title.enAbstract 2578: High regulatory T cells infiltrate within tertiary lymphoid structure restricts response to immune checkpoint blockers in sarcomas
dc.typePosteren_US
dc.identifier.doi10.1158/1538-7445.AM2022-2578en_US
dc.subject.halSciences du Vivant [q-bio]/Canceren_US
dc.subject.halSciences du Vivant [q-bio]/Immunologie/Immunothérapieen_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.conference.titleAmerican association of cancer research 2022en_US
bordeaux.countryusen_US
bordeaux.teamEPICENE_BPHen_US
bordeaux.conference.cityNew Orleansen_US
bordeaux.import.sourcehal
hal.identifierhal-04694521
hal.version1
hal.invitednonen_US
hal.conference.organizerAmerican Association for Cancer Research (AACR)en_US
hal.conference.end2022-04-13
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=PEYRAUD,%20Florent&GUEGAN,%20Jean-Philippe&REY,%20Christophe&PULIDO,%20Marina&BOMPAS,%20Emmanuelle&rft.genre=unknown


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