Abstract PR05: Dgat1 camouflages sexual dimorphism in anti-tumor CD8+ T cell immunity
Bibliographic record
Abstract
Abstract The tumor microenvironment (TME) is enriched in various lipid species that are detrimental to anti-tumor T cell function. However, intratumoral CD8+ T cells were recently shown to require free fatty acids, which are also abundant in the TME, for survival and function. It is not clear whether these free fatty acids regulate transcription or serve as an energy source either directly or through a triacylglyerol (TAG) intermediate step (as in memory CD8+ T cells). Here, we generated mice with T cell-specific deletion of Dgat1, the enzyme that catalyzes the last and rate limiting step in TAG synthesis. We found that the function of Dgat1 in melanoma-infiltrating CD8+ T cells is sexually dimorphic. In female mice, loss of Dgat1 results in much smaller tumors whereas in male mice Dgat1 deficiency limits anti-tumor T cell function. Mechanistically, Dgat1 is required for the survival of stem-cell like Tim3-Slamf6+CD8+ T cells in male mice, but actively decreases their abundance in female mice in a CD8+ T cell-intrinsic manner. Using a number of mouse models we reveal that androgen receptor signaling induces the accumulation of lipid peroxides and the activation of the unfolded protein response in Dgat1-deficient CD8+ T cells. Our study provides insights into a previously unexplored metabolic adaptation of tumor-infiltrating T cells to sex hormones. Citation Format: Alaa Madi, Guoliang Cui. Dgat1 camouflages sexual dimorphism in anti-tumor CD8+ T cell immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr PR05.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".