Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

Autor:	Nelson BH; Deeley Research Centre, BC Cancer, Victoria, Canada., Hamilton PT; Deeley Research Centre, BC Cancer, Victoria, Canada., Phung MT; School of Public Health, University of Michigan, Ann Arbor, United States of America., Milne K; Deeley Research Centre, BC Cancer, Victoria, Canada., Harris B; Deeley Research Centre, BC Cancer, Victoria, Canada., Thornton S; Deeley Research Centre, BC Cancer, Victoria, Canada., Stevens DL; Deeley Research Centre, BC Cancer, Victoria, Canada., Kalaria S; Deeley Research Centre, BC Cancer, Victoria, Canada., Singh K; Deeley Research Centre, BC Cancer, Victoria, Canada., Laumont CM; Deeley Research Centre, BC Cancer, Victoria, Canada., Moss E; Deeley Research Centre, BC Cancer, Victoria, Canada., Alimujiang A; School of Public Health, University of Michiagn, Ann Arbor, United States of America., Meagher NS; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, Australia., Bolithon A; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, Australia., Fereday S; Cancer Genetics and Genomics Laboratory, Peter MaCallum Cancer Centre, Melbourne, Australia., Kennedy CJ; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia., Hendley J; Cancer Genetics and Genomics Laboratory, Peter MaCallum Cancer Centre, Melbourne, Australia., Ariyaratne D; Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia., Alsop K; Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia., Traficante N; Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia., Goode EL; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, United States of America., Karnezis AN; Department of Pathology, UCD School of Medicine, Sacramento, United States of America., Shen H; Epigenetics, Van Andel Institute, Grand Rapids, United States of America., Richardson J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, United States of America., McKinnon Deurloo C; Patient Advocate, United States of America., Chase A; Patient Advocate, United States of America., Grout B; Patient Advocate, United States of America., Doherty JA; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America., Harris HR; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, United States of America., Cushing-Haugen KL; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Anglesio MS; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Heinze K; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Huntsman D; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Talhouk A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Hanley GE; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada., Alsop J; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom., Jimenez-Linan M; Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom., Pharoah PD; Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, United States of America., Boros J; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, Australia., Brand AH; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia., Harnett PR; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia., Sharma R; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia., Hecht JL; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, United States of America., Sasamoto N; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and, Brigham and Women's Hospital and Harvard Medical School, Boston, United States of America., Terry KL; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and, Brigham and Women's Hospital and Harvard Medical School, Boston, United States of America., Karlan BY; Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, United States of America., Lester J; Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, United States of America., Carney ME; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, United States of America., Goodman MT; Cancer Prevention and Control Program, Cedars-Sinai Cancer Center, Cedars-Sinai Medical Center, Los Angeles, United States of America., Hernandez BY; University of Hawaii Cancer Center, Honolulu, United States of America., Wilkens LR; University of Hawaii Cancer Center, Honolulu, United States of America., Behrens S; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Turzanski Fortner R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlang, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany., Bisinotto C; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Candido Dos Reis FJ; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Ghatage P; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Canada., Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada., Elishaev E; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America., Modugno F; Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, United States of America., Cook LS; Epidemiology, School of Public Health, University of Colorado, Aurora, United States of America., Le ND; Cancer Control Research, BC Cancer Agency, Vancouver, Canada., Gentry-Maharaj A; MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom., Menon U; MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom., García MJ; Cancer Biology Department, Sols-Morreale Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain., Rodriguez-Antona C; Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Farrington KM; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada., Kelemen LE; Division of Acute Disease Epidemiology, South Carolina Department of Health and Environmental Control, Columbia, United States of America., Kommoss S; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany., Staebler A; Institute of Pathology and Neuropathology, Tübingen University Hospital, Tübingen, Germany., Garsed DW; Cancer Genetics and Genomics Laboratory, Peter MaCallum Cancer Centre, Melbourne, Australia., Brenton JD; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Piskorz AM; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Bowtell DD; Cancer Genetics and Genomics Laboratory, Peter MaCallum Cancer Centre, Melbourne, Australia., DeFazio A; The Daffodil Centre, The University of Sydney, Sydney, Australia., Ramus SJ; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, Australia., Pike MC; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States of America., Pearce CL; School of Public Health, University of Michigan, Ann Arbor, United States of America.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI:	10.1172/JCI179501
Abstrakt:	Background: Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive ten or more years after standard treatment. Methods: We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared to medium-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intra-epithelial and intra-stromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content. Results: Positive associations with LTS compared to STS were seen for 9/10 immune-cell subsets. In particular, the combination of intra-epithelial CD8+ T cells and intra-stromal B cells showed near five-fold increased odds of LTS compared to STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype. Conclusions: The tumor microenvironment of HGSC long-term survivors is distinguished by the intersection of T and B cell co-infiltration, high epithelial content and C4/Differentiated molecular subtype, features which may inspire new approaches to immunotherapy. Funding: Ovarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; MRC; National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.
Databáze:	MEDLINE
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