Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer Journal Article
| Authors: | Nelson, B. H.; Hamilton, P.; Phung, M. T.; Milne, K.; Harris, B.; Thornton, S.; Stevens, D.; Kalaria, S.; Singh, K.; Laumont, C. M.; Moss, E.; Alimujiang, A.; Meagher, N. S.; Bolithon, A.; Fereday, S.; Kennedy, C. J.; Hendley, J.; Ariyaratne, D.; Alsop, K.; Traficante, N.; Goode, E. L.; Karnezis, A.; Shen, H.; Richardson, J.; McKinnonDeurloo, C.; Chase, A.; Grout, B.; Doherty, J. A.; Harris, H. R.; Cushing-Haugen, K. L.; Anglesio, M.; Heinze, K.; Huntsman, D.; Talhouk, A.; Hanley, G. E.; Alsop, J.; Jimenez-Linan, M.; Pharoah, P. D. P.; Boros, J.; Brand, A. H.; Harnett, P. R.; Sharma, R.; Hecht, J. L.; Sasamoto, N.; Terry, K. L.; Karlan, B.; Lester, J.; Carney, M. E.; Goodman, M. T.; Hernandez, B. Y.; Wilkens, L. R.; Behrens, S.; Fortner, R. T.; Fasching, P. A.; Bisinotto, C.; dos Reis, F. J. C.; Ghatage, P.; Köbel, M.; Elishaev, E.; Modugno, F.; Cook, L.; Le, N.; Gentry-Maharaj, A.; Menon, U.; García, M. J.; Rodriguez-Antona, C.; Farrington, K.; Kelemen, L. E.; Kommoss, S.; Staebler, A.; Garsed, D. W.; Brenton, J. D.; Piskorz, A. M.; Bowtell, D. D. L.; DeFazio, A.; Ramus, S. J.; Pike, M. C.; Pearce, C. L. |
| Article Title: | Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer |
| 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. © 2024, Nelson et al. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; aged; middle aged; primary tumor; human cell; major clinical study; genetics; clinical trial; cd8+ t lymphocyte; t lymphocyte; tumor associated leukocyte; cd8-positive t-lymphocytes; ovarian neoplasms; metabolism; ovary cancer; neoplasm proteins; cohort analysis; cell differentiation; immunofluorescence; pathology; cancer survivor; b lymphocyte; plasma cell; regulatory t lymphocyte; immunology; multicenter study; ovary tumor; tumor protein; cell density; bone marrow cell; immunocompetent cell; programmed death 1 ligand 1; cancer survivors; tumor microenvironment; tumor-associated macrophage; cancer prognosis; humans; human; female; article |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 134 |
| Issue: | 24 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2024-12-16 |
| Start Page: | e179501 |
| Language: | English |
| DOI: | 10.1172/jci179501 |
| PUBMED: | 39470729 |
| PROVIDER: | scopus |
| PMCID: | PMC11645148 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
