| Title: |
Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer |
| Authors: |
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; Fortner, RT; Fasching, PA; 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, DDL; DeFazio, A; Ramus, SJ; Pike, MC; Pearce, CL |
| Source: |
Journal of Clinical Investigation , 134 (24) , Article e179501. (2024) |
| Publisher Information: |
American Society for Clinical Investigation |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Cancer; Cellular immune response; Epidemiology; Immunology; Oncology; Adult; Aged; Female; Humans; Middle Aged; Cancer Survivors; CD8-Positive T-Lymphocytes; Neoplasm Proteins; Ovarian Neoplasms; Tumor Microenvironment |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10204756/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10204756/1/Immunological%20and%20molecular%20features%20of%20the%20tumor%20microenvironment%20of%20long-term%20survivors%20of%20ovarian%20cancer.pdf; https://discovery.ucl.ac.uk/id/eprint/10204756/ |
| Rights: |
open |
| Accession Number: |
edsbas.D2CC602 |
| Database: |
BASE |