Nelson, BH;
Hamilton, P;
Phung, MT;
Milne, K;
Harris, B;
Thornton, S;
Stevens, D;
... Pearce, CL; + view all
(2024)
Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.
Journal of Clinical Investigation
, 134
(24)
, Article e179501. 10.1172/JCI179501.
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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.
| Type: | Article |
|---|---|
| Title: | Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI179501 |
| Publisher version: | https://doi.org/10.1172/jci179501 |
| Language: | English |
| Additional information: | Copyright: © 2024, Nelson et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License |
| Keywords: | 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 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204756 |
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