Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition
Bibliographic record
Abstract
Cancer immunotherapy benefits only a subset of tumor types, underscoring the need for new targets. The protein tyrosine phosphatases PTPN1 and PTPN2 have emerged as promising candidates and stand out for being amenable to small-molecule inhibition. However, competitive inhibitors inhibit both phosphatases equally, leaving a gap in our understanding of their individual contributions. Herein, we dissected the impact of single and double PTPN1/2 deletion on T cell cytotoxicity. Our results show that while PTPN2 functionally dominates over PTPN1, additional deletion of PTPN1 is required for maximal effect. Transcriptomic profiling revealed that dual deficiency synergistically enhanced the IL-10/STAT3 axis, providing mechanistic insight into their cooperative inhibitory roles. Furthermore, we demonstrate that phosphotyrosine mimetic inhibitors of PTPN1, which were already found to be safe in humans, can be repurposed for cancer immunotherapy. This strategy can be used to increase the efficacy of PD-1 blockade and broaden its use to other cancer types.
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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) | 0.000 | 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 | 0.000 |
| 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".