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

Nelson, BH; Hamilton, P; Phung, MT; Milne, K; Harris, B; Thornton, S; Stevens, D; Kalaria, S; Singh, K; Laumont, CM; Moss, E; Alimujiang, A; Meagher, NS; Bolithon, A; Fereday, S; Kennedy, CJ; Hendley, J; Ariyaratne, D; Alsop, K; Traficante, N; Goode, EL; Karnezis, A; Shen, H; Richardson, J; McKinnonDeurloo, C; Chase, A; Grout, B; Doherty, JA; Harris, HR; Cushing-Haugen, KL; Anglesio, M; Heinze, K; Huntsman, D; Talhouk, A; Hanley, GE; Alsop, J; Jimenez-Linan, M; Pharoah, PDP; Boros, J; Brand, AH; Harnett, PR; Sharma, R; Hecht, JL; Sasamoto, N; Terry, KL; Karlan, B; Lester, J; Carney, ME; Goodman, MT; Hernandez, BY; Wilkens, LR; Behrens, S; Turzanski Fortner, R; Fasching, PA; Bisinotto, C; Candido Dos Reis, FJ; Ghatage, P; K&#246;bel, M; Elishaev, E; Modugno, F; Cook, L; Le, N; Gentry-Maharaj, A; Menon, U; Garc&#237;a, MJ; Rodriguez-Antona, C; Farrington, K; Kelemen, LE; Kommoss, S; Staebler, A; Garsed, DW; Brenton, JD; Piskorz, AM; Bowtell, DDL; DeFazio, A; Ramus, SJ; Pike, MC; Pearce, CL

Author(s): Nelson, BH; Hamilton, P; Phung, MT; Milne, K; Harris, B; Thornton, S; Stevens, D; Kalaria, S; Singh, K; Laumont, CM; Moss, E; Alimujiang, A; Meagher, NS; Bolithon, A; Fereday, S; Kennedy, CJ; Hendley, J; Ariyaratne, D; Alsop, K; Traficante, N; Goode, EL; Karnezis, A; Shen, H; Richardson, J; McKinnonDeurloo, C; Chase, A; Grout, B; Doherty, JA; Harris, HR; Cushing-Haugen, KL; Anglesio, M; Heinze, K; Huntsman, D; Talhouk, A; Hanley, GE; Alsop, J; Jimenez-Linan, M; Pharoah, PDP; Boros, J; Brand, AH; Harnett, PR; Sharma, R; Hecht, JL; Sasamoto, N; Terry, KL; Karlan, B; Lester, J; Carney, ME; Goodman, MT; Hernandez, BY; Wilkens, LR; Behrens, S; Turzanski Fortner, R; Fasching, PA; Bisinotto, C; Candido Dos Reis, FJ; Ghatage, P; Köbel, M; Elishaev, E; Modugno, F; Cook, L; Le, N; Gentry-Maharaj, A; Menon, U; García, MJ; Rodriguez-Antona, C; Farrington, K; Kelemen, LE; Kommoss, S; Staebler, A; Garsed, DW; Brenton, JD; Piskorz, AM; Bowtell, DDL; DeFazio, A; Ramus, SJ; Pike, MC; Pearce, CL;
Details: Publication Year 2024-10-29,Volume 134,Issue #24,Page e179501
Journal Title: Journal of Clinical Investigation
Publication Type: Research article
Abstract: 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.
Publisher: American Society for Clinical Investigation
Keywords: Humans; Female; *Tumor Microenvironment/immunology; *Ovarian Neoplasms/immunology/pathology/genetics; *Cancer Survivors; Middle Aged; Aged; CD8-Positive T-Lymphocytes/immunology/pathology; Neoplasm Proteins/genetics/immunology/metabolism; Adult; Cancer; Cellular immune response; Epidemiology; Immunology; Oncology
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1172/jci179501
Open Access at Publisher's Site: https://doi.org/10.1172/jci179501
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-07 06:20:59

Last Modified: 2025-01-07 06:21:10