Reinvigoration of translational activity in dysfunctional T cells initiates the early intratumoral response to PD-1 blockade
Bibliographic record
Abstract
Abstract T cells are key effectors of antitumor responses elicited by PD-1 blockade. However, it remains elusive by which mechanism(s) PD-1 blockade initiates T cell-driven antitumor immunity in cancer tissues. Here, we dissect early T cell reactivation upon anti-PD-1 in patient-derived tumor fragments. Using bispecific antibodies to target anti-PD-1 to individual T cell subsets, we demonstrate that intratumoral CD8 + and CD4 + T cells can independently drive immune remodeling of the tumor microenvironment. The CD8 + and CD4 + T cells that respond to anti- PD-1 exhibit a shared dysfunctional gene program, characterized by tumor-reactivity, terminal exhaustion, effector capacity, and reduced translational activity. Notably, rather than acting through transcriptional rewiring, anti-PD-1 reinvigorates dysfunctional T cells by overcoming this translational barrier, resulting in restored effector function. Altogether, these results reveal dysfunctional T cells as initiators of early tissue responses to PD-1 blockade and identify a novel mode of their therapeutic reinvigoration through restoration of translational control. One Sentence Summary Translational reactivation of tumor-residing dysfunctional T cells drives early intratumoral immune activity upon PD-1 blockade.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".