Citations 1
Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer
Hamilton, Phineas T. , Phung, Minh Tung , Stevens, Donald L.I., Kalaria, Shreena , Laumont, Céline M. , Moss, Elena, Alimujiang, Aliya , Meagher, Nicola S. , Hendley, Joy , Goode, Ellen L. , Shen, Hui , Richardson, Jean , Deurloo, Cindy McKinnon, Chase, Anne, Grout, Bronwyn, Cushing‐Haugen, Kara L. , Anglesio, Michael S. , Huntsman, David G. , Talhouk, Aline , Hanley, Gillian E. , Alsop, Jennifer , Jimenez-Linan, Mercedes , Boros, Jessica , Brand, Alison H. , Sharma, Raghwa , Hecht, Jonathan L. , Sasamoto, Naoko , Terry, Kathryn L. , Lester, Jenny, Carney, Michael E. , Goodman, Marc T. , Fasching, Peter A., Bisinotto, Christiani, Le, Nhu D. , Menon, Usha , García, María J. , Rodríguez‐Antona, Cristina , Farrington, Kyo , Kelemen, Linda E. , Kommoss, Stefan , Staebler, Annette , Garsed, Dale W. , Piskorz, Anna , Bowtell, David D.L. , Ramus, Susan J. , Pike, Malcolm C., Pearce, Celeste Leigh , Ramus, Susan J , Rodríguez-Antona, Cristina , Menon, Usha , Anglesio, Michael S , Brand, Alison H , Bowtell, David D , Garsed, Dale W , Goodman, Marc T , Phung, Minh Tung , Nelson, Brad H. , Milne, Katy , Harris, Bronwyn, Thornton, Shelby , Singh, Karanvir , Bolithon, Adelyn , Fereday, Sián , Kennedy, Catherine J. , Ariyaratne, Dinuka , Alsop, Kathryn , Traficante, Nadia , Karnezis, Anthony N. , Chase, Anne, Doherty, Jennifer A. , Harris, Holly R. , Heinze, Karolin , Pharoah, Paul D.P. , Harnett, Paul R. , Karlan, Beth Y. , Hernandez, Brenda Y. , Wilkens, Lynne R. , Behrens, Sabine , Fortner, Renée T. , Reis, Francisco José Cândido dos , Ghatage, Prafull , Köbel, Martin , Elishaev, Esther , Modugno, Francesmary , Cook, Linda S. , Gentry‐Maharaj, Aleksandra , Brenton, James D. , DeFazio, Anna
Journal of Clinical Investigation | October 29, 2024 | Volume: 134 | Issue: 24 | Pages: No page available
BACKGROUND Despite 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. 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 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. RESULTS Positive 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. CONCLUSION The 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. 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; 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.