Abstract B76: CD8+FoxP3+ T cells: A new player in the immune response to ovarian cancer.
Bibliographic record
Abstract
Abstract Introduction: Tumor-infiltrating lymphocytes (TIL) are an important prognostic indicator in high-grade serous ovarian carcinoma (HGSC). Certain types of TIL (in particular CD8+ effector T cells) predict better outcomes, whereas others (most notably CD4+CD25+FoxP3+ regulatory T cells or Tregs) predict worse outcomes. An unconventional subset of CD8+FoxP3+ T cells has been widely reported in autoimmunity. While the functional significance of CD8+FoxP3+ TIL remains poorly understood, in a murine tumor model they were associated with effective anti-tumor responses. Hypothesis: CD8+FoxP3+ TIL are present in HGSC and correlate with effector TIL and increased patient survival. Experimental Design: Multi-parameter flow cytometry and immunohistochemistry (IHC) were performed on cohorts of 12 and 45 primary HGSC specimens, respectively, to enumerate and locate CD8+FoxP3+ TIL. For IHC, intraepithelial versus stromal location was determined by staining adjacent sections for the epithelial marker cytokeratin. Multi-color staining was resolved using the Nuance™ multispectral imaging system in conjunction with Metamorph software. Survival analysis will be performed by staining a cohort of 200 cases of HGSC. Results: By flow cytometry, CD8+FoxP3+ cells were found in variable proportions between HGSC cases, representing 1.3 - 7.9% of CD8+ TIL and 1.3 - 25.8% of FoxP3+ TIL. By IHC, CD8+FoxP3+ TIL were found together with CD8+FoxP3- and CD4+FoxP3+ TIL in epithelial and stromal tumor regions and represented up to 19% of the FoxP3+ population. Interestingly, the majority of CD8+FoxP3+ TIL were also found to be TIA-1+KI67-, consistent with an active role in the anti-tumor response. Conclusions: CD8+FoxP3+ TIL are a component of the host immune response to HGSC. Survival analysis is ongoing and will determine whether CD8+FoxP3+ T cells enhance or inhibit tumor immunity. Improved understanding of this new TIL subset will inform future immunotherapy strategies for this challenging malignancy. Citation Format: Sara E.F. Kost, Ronald J. deLeeuw, Brad H. Nelson. CD8+FoxP3+ T cells: A new player in the immune response to 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 B76.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".