PD-1 endocytosis unleashes the cytolytic potential of checkpoint blockade in tumor immunity
Bibliographic record
Abstract
PD-1 immune checkpoint blockade (ICB) is a key cancer treatment. While blocking PD-1 binding to ligand is known, the role of internalization in enhancing ICB efficacy is less explored. Our study reveals that PD-1 internalization helps unlock ICB's full potential in cancer immunotherapy. Anti-PD-1 induces 50%–60% surface PD-1 internalization from human and mouse cells, leaving low to intermediate levels of resistant receptors. Complexes then appear in early and late endosomes. Both CD4 and CD8 T cells, especially CD8 + effectors, are affected. Nivolumab outperforms pembrolizumab in human T cells, while PD-1 internalization requires crosslinking by bivalent antibody. While mono- and bivalent anti-PD-1 inhibit tumor growth with CD8 tumor-infiltrating cells expressing increased granzyme B, bivalent antibody is more effective where the combination of steric blockade and endocytosis induces greater CD8 + T cell tumor infiltration and the expression of the cytolytic pore protein, perforin. Our findings highlight an ICB mechanism that combines steric blockade and PD-1 endocytosis for optimal checkpoint immunotherapy.
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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) | 0.001 | 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 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".