Abstract A15: Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer
Bibliographic record
Abstract
Abstract Triple negative breast cancer (TNBC), defined as tumors lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are especially difficult to treat effectively. While ER+ and HER2+ breast cancer subtypes can be treated with Tamoxifen and Herceptin, respectively, there are no targeted therapies for TNBC patients. Furthermore, while only 20-30% of TNBC patients respond to chemotherapy in the neoadjuvant setting, overall outcome remains poor for non-responding patients. However, mounting evidence suggests that immune-checkpoint inhibitor immunotherapies may be especially promising for TNBC patients. We and others have shown that the presence of CD8+ T cells, a crucial component of the cytotoxic arm of the adaptive immune response, is a sign of good clinical outcome in TNBC patients. However, good outcome only correlates with CD8+ T cell invasion of the tumor parenchyma. Here we show that some patients have an accumulation of CD8+ T cells in the surrounding tumor-associated stroma, but not the tumor epithelium, and these patients responded as poorly as patients with no CD8+ T cells at all. Yet how cancer associated fibroblasts (CAFs), a dominant cell type of the tumor-associated stroma, affects CD8+ T cell invasion into the tumor epithelium is still poorly understood. To identify potential stroma-dependent mechanisms that potentiate or inhibit CD8+ T cells invasion into the tumor epithelium, we performed gene expression profiling of laser-capture microdissected tumor-associated stroma (and matched epithelium) from 56 TNBC cases. Here we identify several key stromal features that may explain the accumulation of CD8+ T cells outside of the tumor epithelium. Preliminary data by immunohistochemistry and immunofluorescence validate some key stromal features and decipher the implication of other immune cell types in CD8+ T cells lack of tumor epithelium infiltration. These key stromal features that impair CD8+ T cell infiltration into the tumor in some patients might explain the relative low efficiency of immunotherapies in TNBC patients (20% of patients respond). One could speculate that targeting these key stromal features would allow a significant CD8+ T cell infiltration into the tumor and thus sensitize patients to immunotherapies. Citation Format: Tina Gruosso, Mathieu Gigoux, Nicholas Bertos, Sadiq Saleh, Atilla Omeroglu, Dongmei Zuo, Hong Zhao, Margarita Souleimanova, Valerie Weaver, Sarkis Meterissian, Michael Hallett, Morag Park. Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A15.
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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 | 0.000 | 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) | 0.002 | 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".