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 PD, 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, Fortner RT, Fasching P, Bisinotto C, dos Reis FJC, 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 DD, DeFazio A, Ramus SJ, Pike MC, Pearce CL (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 134

Article Number: e179501

Journal Issue: 24

DOI: 10.1172/JCI179501

Abstract

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.

Authors with CRIS profile

Involved external institutions

British Columbia Cancer Agency Canada (CA) University of Michigan United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Peter MacCallum Cancer Centre Australia (AU) Westmead Institute for Medical Research Australia (AU) Mayo Clinic United States (USA) (US) University of California Davis (UCDAVIS) United States (USA) (US) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) University of Calgary Canada (CA) University of Pittsburgh United States (USA) (US) University of Colorado Anschutz Medical Campus United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Cambridge United Kingdom (GB) Instituto de Investigaciones Biomédicas Alberto Sols (IIBM) Spain (ES) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Universitätsklinikum Tübingen Germany (DE) University of Sydney (USYD) Australia (AU) Memorial Sloan Kettering Cancer Center United States (USA) (US) South Carolina Department of Health and Environmental Control United States (USA) (US) Van Andel Institute United States (USA) (US) Keck School of Medicine of USC United States (USA) (US) Huntsman Cancer Institute United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) University of British Columbia Canada (CA) Addenbrooke's Hospital United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Westmead Hospital Australia (AU) Harvard University United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE)

How to cite

APA:

Nelson, B.H., Hamilton, P., Phung, M.T., Milne, K., Harris, B., Thornton, S.,... Pearce, C.L. (2024). Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer. Journal of Clinical Investigation, 134(24). https://doi.org/10.1172/JCI179501

MLA:

Nelson, Brad H., et al. "Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer." Journal of Clinical Investigation 134.24 (2024).

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