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

Autor: Nelson BH; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Hamilton P; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Phung MT; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Milne K; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Harris B; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Thornton S; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Stevens D; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Kalaria S; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada., Singh K; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Laumont CM; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Moss E; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Alimujiang A; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA., Meagher NS; School of Clinical Medicine, University of New South Wales (NSW) Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia., Bolithon A; School of Clinical Medicine, University of New South Wales (NSW) Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia., Fereday S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Kennedy CJ; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Hendley J; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Ariyaratne D; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Alsop K; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Traficante N; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia., Goode EL; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA., Karnezis A; Department of Pathology, University of California Davis School of Medicine, Sacramento, California, USA., Shen H; Van Andel Institute, Grand Rapids, Michigan, USA., Richardson J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.; Patient advocate., McKinnonDeurloo C; Patient advocate., Chase A; Patient advocate., Grout B; Patient advocate., Doherty JA; Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA., Harris HR; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Epidemiology, University of Washington, Seattle, Washington, USA., Cushing-Haugen KL; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Anglesio M; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, Canada., Heinze K; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, Canada., Huntsman D; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada., Talhouk A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, Canada., Hanley GE; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, 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, West Hollywood, California, USA., Boros J; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Brand AH; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Harnett PR; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Crown Princess Mary Cancer Centre and., Sharma R; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Westmead Hospital, Sydney, New South Wales, Australia.; Western Sydney University, Sydney, New South Wales, Australia., Hecht JL; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA., Sasamoto N; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Terry KL; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Karlan B; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California, USA., Lester J; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California, USA., Carney ME; Department of Obstetrics and Gynecology, John A. Burns School of Medicine University of Hawaii, Honolulu, Hawaii, USA., Goodman MT; Cancer Prevention and Control Program, Cedars-Sinai Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California, USA., Hernandez BY; University of Hawaii Cancer Center, Honolulu, Hawaii, USA., Wilkens LR; University of Hawaii Cancer Center, Honolulu, Hawaii, USA., 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.; Department of Research, Cancer Registry of Norway, Oslo, Norway., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, 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, Alberta, Canada., Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada., Elishaev E; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Modugno F; Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, Pennsylvania, USA., Cook L; Epidemiology, School of Public Health, University of Colorado, Aurora, Colorado, USA.; Community Health Sciences, University of Calgary, Calgary, Alberta, Canada., Le N; Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada., Gentry-Maharaj A; MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology and.; Department of Women's Cancer, Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, United Kingdom., Menon U; MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology and., 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 Center (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Farrington K; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada., Kelemen LE; Division of Acute Disease Epidemiology, South Carolina Department of Health and Environmental Control, Columbia, South Carolina, USA., Kommoss S; Department of Women's Health and., Staebler A; Institute of Pathology and Neuropathology, Tuebingen University Hospital, Tuebingen, Germany., Garsed DW; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 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; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., DeFazio A; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Ramus SJ; School of Clinical Medicine, University of New South Wales (NSW) Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia., Pike MC; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Pearce CL; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2024 Oct 29; Vol. 134 (24). Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1172/JCI179501
Abstrakt: BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe 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 with mid-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 intraepithelial and intrastromal 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.RESULTSPositive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8+ T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with 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.CONCLUSIONThe tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy.FUNDINGOvarian 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; Medical Research Council (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