Immune predictors of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.

Autor:	Grau Bejar JF; Gynecological Oncology Programme, Vall d'Hebron Institute of Oncology, Barcelona, Spain.; Gynecological Cancer Translational Research Laboratory, INSERM U981, Gustave Roussy Institute, Villejuif, France., Yaniz Galende E; Gynecological Cancer Translational Research Laboratory, INSERM U981, Gustave Roussy Institute, Villejuif, France., Zeng Q; Laboratoire d'Informatique Paris Descartes (LIPADE), Université Paris Cité, Paris, France.; Centre d'Histologie, Imagerie cellulaire et Cytométrie (CHIC), Centre de Recherche des Cordeliers, Centre de Recherche des Cordeliers, Paris, France., Genestie C; Pathology Department, Gustave Roussy Institute, Villejuif, France., Rouleau E; Department of Medical Biology and Pathology, Cancer Genetics Laboratory, Gustave Roussy Institute, Villejuif, France., de Bruyn M; Obstetrics & Gynecology, University of Groningen Faculty of Medical Sciences, Groningen, The Netherlands., Klein C; Centre d'Histologie, Imagerie cellulaire et Cytométrie (CHIC), Centre de Recherche des Cordeliers, Centre de Recherche des Cordeliers, Paris, France., Le Formal A; Gynecological Cancer Translational Research Laboratory, INSERM U981, Gustave Roussy Institute, Villejuif, France., Edmond E; Experimental and Translational Pathology Platform (PETRA), AMMICa Inserm US23/UAR CNRS 3655, Gustave Roussy Institute, Villejuif, France., Moreau M; Department of Medical Biology and Pathology, Cancer Genetics Laboratory, Gustave Roussy Institute, Villejuif, France., Plat A; Obstetrics & Gynecology, University of Groningen Faculty of Medical Sciences, Groningen, The Netherlands., Gouy S; Department of Gynecologic Surgery, Department of Surgery, Gustave Roussy Institute, Villejuif, France., Maulard A; Department of Gynecologic Surgery, Department of Surgery, Gustave Roussy Institute, Villejuif, France., Pautier P; Gynecological Cancer Unit, Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France., Michels J; Gynecological Cancer Unit, Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France., Oaknin A; Gynecological Oncology Programme, Vall d'Hebron Institute of Oncology, Barcelona, Spain., Colomba-Blameble E; Gynecological Cancer Unit, Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France., Leary A; Gynecological Cancer Translational Research Laboratory, INSERM U981, Gustave Roussy Institute, Villejuif, France alexandra.leary@gustaveroussy.fr.; Gynecological Cancer Unit, Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Jul 01; Vol. 12 (7). Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1136/jitc-2024-009143
Abstrakt:	Background: Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) can derive great benefit from immune checkpoint inhibitors (ICI). However not all responses and predictors of primary resistance are lacking. Methods: We compared the immune tumor microenvironment of MMRd EC ICI-responders (Rs) and ICI non-responders (NRs), using spatial multiplexed immune profiling and unsupervised hierarchical clustering analysis. Results: Overall, NRs exhibited drastically lower CD8 + , absent terminally differentiated T cells, lack of mature tertiary lymphoid structures and dendritic cells, as well as loss of human leukocyte antigen class I. However, no single marker could predict R versus NR with confidence. Clustering analysis identified a combination of four immune features that demonstrated that accurately predicted ICI response, with a discriminative power of 92%. Finally, 80% of NRs lacked programmed death-ligand 1, however, 60% exhibited another actionable immune checkpoint (T-cell immunoglobulin and mucin containing protein-3, indoleamine 2,3-dioxygenase 1, or lymphocyte activation gene 3). Conclusions: These findings underscore the potential of immune tumor microenvironment features for identifying patients with MMRd EC and primary resistance to ICI who should be oriented towards trials testing novel immunotherapeutic combinations. Competing Interests: Competing interests: JFGB reports personal honoraria as speaker from GSK and AstraZeneca; personal fees for travel/accommodation from GSK and AstraZeneca. AL reports institutional funding from AstraZeneca, Clovis, GSK, MSD, Merck Serono, Ability, Zentalis, Agenus, Iovance, Sanofi, Roche, OSEimmuno, BMS, Blueprint; personal fees for consulting or advisory role from Zentalis Funded research from Zentalis. JM reports personal fees for consulting or advisory role from Brenus Pharma, GSK, Regeneron; personal fees for travel/accommodation from GSK and MSD; Funded research from MSD. EC-B reports personal fees for consulting or advisory role from Ipsen, BMS, Merck, GSK, Sanofi; personal fees for travel/accommodation from Ipsen, BMS, Pfizer. AO reports personal fees for advisory board membership from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, DaIichi Sankyo, Debiopharm International, Deciphera Pharmaceuticals, Eisai, Exelisis, EMD Serono, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, Merck Sharps & Dohme de España, SA, Mersana Therapeutics, Myriad Genetics, Novocure, OneXerna Therapeutics, Inc., PharmaMar, Regeneron, Sattucklabs, Seagen, Sutro Biopharma and Zentalis; personal fees for travel/accommodation from AstraZeneca, PharmaMar and Roche; institutional funding from AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Regeneron Pharmaceuticals and Tesaro Inc.; non-remunerated roles at ESMO (member, Officer, Co-Chair of the ESMO Gynaecological Cancers Congress 2023-2025, Chair of the Gynaecological Track ESMO 2019, Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022, member of the Gynaecological Cancers Faculty and Subject Editor for the Gynaecological Clinical Practice Guidelines); a non-remunerated role at GCIG (member and Cervix Cancer Chair on behalf of GEICO); and membership of ASCO, GOG and SEOM. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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