ArticleJournal for immunotherapy of cancer2025
Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunosuppressive roles of pericytes in cancer disease: insights from a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- An immune responsive tumor microenvironment imprints into PBMCs and predicts outcome in advanced pancreatic cancer: lessons from the PREDICT trial.Molecular cancer · 2025Trial
- Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.Oncoimmunology · 2026Review
- Review
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- Targeting regulatory T cells in the prostate cancer microenvironment: From mechanisms to therapeutics (Review).Molecular medicine reports · 2026Review
- Identification of prognostic genes and development of a risk model for pancreatic cancer based on hypoxia- and lipid metabolism-related genes.Discover oncology · 2026Article
- The interplay between tumor-intrinsic KRT6A and host-derived immune-nutritional status (PNI) defines prognosis in resectable PDAC.Scientific reports · 2026Article
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Hypoxic-immune axis orchestrates metastatic dissemination via HIF isoform imbalance in pancreatic neuroendocrine tumors.iScience · 2026Article
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- Elevated Transglutaminase-2 in SOX10-Deficient Melanoma Promotes Tumor Onset and Decreases Intratumoral CD4+ T Cells.Cancer research · 2025Article
- Harnessing nanoprodrugs to enhance cancer immunotherapy: overcoming barriers to precision treatment.Materials today. Bio · 2025Review
- Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.Journal for immunotherapy of cancer · 2025Article
- Successful rescue of PD-1 inhibitor-induced TEN by vincristine combination therapy: a case report and literature review.Frontiers in oncology · 2025Article
- Transglutaminase 7 Silencing Inhibits Proliferation and Modulates Inflammatory and Apoptotic Markers in Testicular Germ Cell Tumors.Oncology research · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.
methodsWe used an unbiased screening approach of T cell resistant and sensitive murine KPC (
resultsWe identified transglutaminase 2 (TGM2) as a mediator of T cell suppression in PDAC. We report that high levels of TGM2 expression in patients' tumors correlate with immunosuppressive signatures and poor overall survival. We found that TGM2 regulates vesicle trafficking by modulating microtubule network density and dynamics in pancreatic cancer cells, thus facilitating the secretion of immunosuppressive cytokines, which impair effector T cell functionality. In TGM2-expressing PDOs, pharmacological TGM2 inhibition or treatment with nocodazole increased T cell-mediated apoptosis. Also, pretreatment of TGM2
conclusionsThese findings indicate that targeting microtubular function therapeutically may enhance antitumor T cell responses by impacting activity of immunosuppressive cytokines in the PDAC microenvironment.
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