Abstract PR03: Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma
Bibliographic record
Abstract
Abstract Response to immunotherapy remains less than 20% for Oral Cavity Squamous Cell Carcinoma (OSCC). The poor response is in part due to dysfunctional cytotoxic T cell activity resulting from terminal exhaustion as a response to chronic exposure to tumor antigen. New strategies are needed to sensitize OSCC to immunotherapy to improve response rates and overall survival. Stimulation of muscarinic receptors by Acetylcholine (Ach), the primary neurotransmitter of the parasympathetic nervous system, restrains pancreatic and breast cancer but promotes gastric and late stage prostate cancer. The role of cholinergic signaling in OSCC is unknown. Ach can be secreted from non-neuronal tissues, including lymphocytes, which are abundant in the OSCC microenvironment. These lymphocytes express choline acetyltransferase (ChaT), the enzyme catalyzing the rate limiting step of Ach production and are important in maintaining chronic anti-viral immune responses. Our objective is to uncover the role of these Ach secreting T cells in mediating the anti-tumor immune response in OSCC. We utilized the 4MOSC1 and 4MOSC2 orthotopic OSCC tumor model. Orthotopic tumors were generated in recipient mice with impaired Ach-muscarinic signaling. ChaT+ CD8+ T cells were amplified in the tumor microenvironment and in vitro after activation. Inhibition of Ach-muscarinic signaling in the tumor immune microenvironment (TIME) accelerated tumor growth kinetics and was associated with loss of tumor infiltrating lymphocytes (TILs). Analysis of T cell activation states in TILs and after in vitro activation demonstrated that disruption of Ach-muscarinic signaling promotes differentiation of effector T lymphocytes at the expense of central memory. These data suggest that the Ach-muscarinic axis promotes CD8+ T cell infiltration and maintains T cell memory in the TIME supporting long term anti-tumor immune responses. Citation Format: Ruth A. White. Cholinergic modulation of tumor infiltrating lymphocytes in oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR03.
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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) | 0.003 | 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".