Dataset Information

Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer.

ABSTRACT:

Background

Studies have shown that tumor infiltrating lymphocyte (TILs) abundance is associated with overall survival in patients with high-grade serous ovarian cancer (HGSOC); however, the role of the spatial contexture and organization of TILs is less clear.

Methods

We evaluated the association between spatial architecture of T cells and survival in women with HGSOC from three large epidemiological studies in which tumors were analyzed by multiplex immunofluorescence (N = 433). A Ripley's K measure was used to determine the spatial clustering. Cox proportional hazards models assessed the association of spatial clustering with overall survival.

Results

We found having high abundance and low spatial clustering of CD3⁺ TILs and CD3⁺CD8⁺ cytotoxic T lymphocytes (CTLs) was associated with improved overall survival (TILs HR=0.61, 95% CI 0.46-0.81, P=0.0005; CTLs HR=0.59, 95% CI 0.44-0.80, P=0.0007). Models with abundance and spatial information outperformed models with only the abundance levels (TILs P=0.002, CTLs P=0.00007).

Conclusion

High abundance of TILs and CTLs that are spatially distributed across the tumor was associated with better survival, replicating our work in non-Hispanic Black women, and supporting that the spatial architecture of the tumor microenvironment is an important predictor of survival in HGSOC.

SUBMITTER: Soupir AC

PROVIDER: S-EPMC10827255 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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WITHDRAWN: Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer.

Soupir Alex C AC Townsend Mary K MK Hathaway Cassandra A CA Nguyen Jonathan J Moran Segura Carlos C Saeed-Vafa Daryoush D Ospina Oscar E OE Peres Lauren C LC Conejo-Garcia Jose R JR Terry Kathryn L KL Tworoger Shelley S SS Fridley Brooke L BL

medRxiv : the preprint server for health sciences 20240228

The authors have withdrawn their manuscript owing to incorrect handling of multiple measures in the survival analyses. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. ...[more]

PMID: 38293174

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Project description:ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.Conclusions and relevanceThis study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.