High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells
Bibliographic record
Abstract
High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During inflammation, epithelial cells can be induced to express MHC-II and function as accessory APCs. Utilizing RNA-seq data from over 500 HNSCC patients from The Cancer Genome Atlas, we determined the impact of HPV-status on the expression of MHC-II genes and related genes involved in their regulation, antigen presentation, and T-cell co-stimulation. Expression of virtually all MHC-II genes was significantly upregulated in HPV+ carcinomas compared to HPV− or normal control tissue. Similarly, genes that encode products involved in antigen presentation were also significantly upregulated in the HPV+ cohort. In addition, the expression of CIITA and RFX5—regulators of MHC-II—were significantly upregulated in HPV+ tumors. This coordinated upregulation of MHC-II genes was correlated with higher intratumoral levels of interferon-gamma in HPV+ carcinomas. Furthermore, genes that encode various co-stimulatory molecules involved in T-cell activation and survival were also significantly upregulated in HPV+ tumors. Collectively, these results suggest a previously unappreciated role for epithelial cells in antigen presentation that functionally contributes to the highly immunogenic tumor microenvironment observed in HPV+ HNSCC.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".