Programmed cell death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) expression in PD‐1 inhibitor‐associated colitis and its mimics
Bibliographic record
Abstract
AIMS: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced malignancies by boosting immune-mediated destruction of neoplastic cells, but are associated with side effects stemming from generalised immune system activation against normal tissues. Checkpoint ligand expression in non-tumoral cells of tissues affected by immune-related adverse effects has been described in ICI-associated hypophysitis, myocarditis, and acute interstitial nephritis. We aimed to investigate the tissue expression of the immune checkpoint receptor programmed cell death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), in PD-1 inhibitor-associated colitis (PD1i colitis). METHODS AND RESULTS: PD-1 and PD-L1 immunohistochemical expression levels were analysed in 15 cases of PD1i colitis and potential mimics-infectious colitis and inflammatory bowel disease (IBD). Increased epithelial expression of PD-L1 was observed in PD1i colitis as compared with normal colon and infectious colitis, but the expression level was lower than that in IBD. Conversely, PD-1 expression in inflammatory cells was higher in infectious colitis, intermediate in IBD, and minimal or absent in normal colon and in patients receiving PD-1 inhibitors. CONCLUSIONS: Although our results do not justify the use of PD-L1 as a discriminatory marker of PD1i colitis against other entities within the differential diagnosis, they support the concept that PD1i colitis and IBD have similar pathogenetic mechanisms. They also highlight the fact that PD-L1 epithelial overexpression is a commonly used mechanism of the gastrointestinal tract mucosa to protect itself from inflammatory-mediated damage resulting from different aetiologies, which probably underpins the high incidence of gastrointestinal immune-related adverse effects in patients receiving ICI therapies, in whom this mechanism is disrupted.
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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) | 0.000 | 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".