Abstract B032: CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy
Bibliographic record
Abstract
Abstract Oropharyngeal squamous cell carcinoma (OPSCC) is a prevalent subtype of head and neck cancer representing one of the largest diagnosed malignancies worldwide. A distinct subtype of OPSCC induced by Human Papilloma Virus (HPV) is well known to favor beneficial clinical outcomes in cancer treatment compared to HPV-negative OPSCCs. However, HPV-positive OPSCCs in the context of immunotherapy remains unclear, as no distinct benefits are observed in clinical trials. In this study, we performed single-cell RNA and T cell receptor sequencing analyses of 20 tumor samples to dissect the cellular and molecular factors associated with viral infection and immunotherapy outcome. We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. This finding suggests heterogeneity of malignant cells negates immunotherapy response in HPV-positive OPSCCs. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed significant association with dampened antitumor activity in HPV-positive OPSCC patients, which may explain their clinical heterogeneity. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Validation in an independent cohort confirms enhanced tertiary lymphoid structure activity in HPV-positive OPSCCs. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade confirmed an inverse correlation between the density of CD161+ Trm and changes in tumor size. These results suggest that targeted inhibition of CD161 in Trm may augment immunotherapy efficacy in HPV-positive oropharyngeal cancers. Citation Format: Junha Cha, Dahee Kim, Gamin Kim, Jae-Won Cho, Euijeong Sung, Seungbyn Baek, Min Hee Hong, Chang Gon Kim, Nam Suk Sim, Hyun Jun Hong, Jung Eun Lee, Martin Hemberg, Seyeon Park, Sun Ock Yoon, Sang-Jun Ha, Yoon Woo Koh, Hye Ryun Kim, Insuk Lee. CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy [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 B032.
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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 | 0.004 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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 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".