ArticleNature communications2025
Targeting TNK2/ACK1 reverses the immunosuppressive tumor microenvironment and synergizes with immunochemotherapy in pancreatic cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
3 citing papers in PubMed.
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Palmaturbine Inhibits Pancreatic Ductal Adenocarcinoma by Suppressing the JAK2/STAT3 Signaling Pathway.International journal of molecular sciences · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to its aggressive nature and limited treatment options, with the efficacy of immunotherapy constrained by a uniquely immunosuppressive tumor microenvironment (TME). In this study, we identify TNK2/ACK1 as a key regulator of the immunosuppressive TME in PDAC. TNK2/ACK1 is significantly upregulated in PDAC, at least in part via gene amplification and KRAS-G12 mutations. Mechanistically, TNK2/ACK1 directly phosphorylates and activates STAT5A to induce the expression of the immune checkpoint HVEM, which suppresses CD8⁺ T-cell function via its receptor BTLA. Pharmacologic targeting of TNK2/ACK1 with AIM100 or (R)-9b enhances CD8⁺ T-cell activation and cytotoxicity while reprogramming the TME. Furthermore, combining TNK2/ACK1 inhibitors with anti-PD-1 immunotherapy or with nab-paclitaxel plus gemcitabine demonstrates promising antitumor efficacy in both allograft and spontaneous PDAC models. Overall, our findings reveal a mechanism of immune evasion and provide a potential framework for developing tailored immunotherapeutic strategies in PDAC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.