Abstract B88: Clinical significance of FOXP3+ T cell heterogeneity in ovarian cancer.
Bibliographic record
Abstract
Abstract Background: CD8+ tumor-infiltrating lymphocytes (TIL) are associated with survival in ovarian cancer. A second subpopulation of TIL – defined by FoxP3 expression – has been reported to inhibit tumor immunity, resulting in decreased patient survival. However, recent studies by our lab and others have challenged this paradigm by showing that FoxP3+ T cells, in some patient cohorts, are associated with favorable prognosis. Hypothesis: FoxP3 expression encompasses heterogeneous populations of effector and regulatory T cells that vary in proportion between patients and provide differential prognostication. Methodology: We used multi-parameter flow cytometry to assess CD25, CD28, CD39, CD45RO, CD103, CD127, CTLA-4, CCR4, CCR7, GITR, Helios, ICOS, IFN-gamma, and PD-1 in CD3+CD4+CD8-FoxP3+ TIL in 12 patients with high-grade serous ovarian cancer (HGSC). CD4 and CD8 expression within FoxP3+ TIL was assessed by four channel multi-parameter immuno-histochemistry (mIHC). CD8-FoxP3+ TIL were assessed for CD25 and CD39 expression by mIHC. Survival analysis will be assessed via Kaplan-Meier plots, log-rank tests and Cox regression analyses. Results: Consistent with prior reports, flow cytometry revealed that FoxP3 was expressed predominantly by CD4+ TIL. All CD4+FoxP3+ cells also expressed CD28, CD45RO, ICOS and CTLA-4, while they lacked expression of CD103 and IFN-gamma. However, we observed highly varied expression of regulatory T cell markers, including CD25, CD39, and GITR. Furthermore, on average, 4% (range 0-25%) of FoxP3+ TIL were CD8+. TCR spectratyping revealed similar TCR Vβ usage patterns between FoxP3- and FoxP3+ TIL. Although mIHC confirmed the variable expression of CD39 in CD8-FoxP3+ TIL, the expression of CD39 by a portion of HGSC tumors eliminated our ability to assess the clinical significance of this subset. The clinical significance of CD25 expression in CD8-FoxP3+ TIL is currently being analyzed in 245 cases of HGSC by mIHC. Conclusions: FoxP3+ TIL demonstrate profound phenotypic heterogeneity within and between HGSC patients. FoxP3- and FoxP3+ TIL appear to be clonally related, suggesting their distinct phenotypes reflect microenvironmental influences rather than developmental origin or antigen specificity. The variable expression of CD25 and CD39 may be of importance in defining clinically important FoxP3+ TIL subsets. Further study of FoxP3+ TIL subpopulations in HGSC is required to better understand their contributions to tumor immunity and patient survival. Citation Format: Ronald J. deLeeuw, Sara E. Kost, Brad H. Nelson. Clinical significance of FOXP3+ T cell heterogeneity in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B88.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".