Pancreatic cancer harbors a diverse T cell arsenal—including unexpected viral and stress antigen targets.
Single-cell transcriptomics + functional TCR characterization in murine pancreatic cancer found substantial diversity of tumor-reactive TCR clonotypes. Most reactive TCRs recognized syngeneic tumors across tissue types. Three T cell epitope classes were identified: a neoantigen, an endogenous…
Pancreatic cancer harbors a diverse T cell arsenal—including unexpected viral and stress antigen targets.
Single-cell transcriptomics + functional TCR characterization in murine pancreatic cancer found substantial diversity of tumor-reactive TCR clonotypes. Most reactive TCRs recognized syngeneic tumors across tissue types. Three T cell epitope classes were identified: a neoantigen, an endogenous retroviral epitope, and a cell stress-induced autoantigen.
Key Findings
- Substantial diversity of tumor-reactive TCR clonotypes in pancreatic cancer
- Most tumor-reactive TCRs recognized syngeneic tumors across tissue types
- Three epitope classes: neoantigen, endogenous retroviral, and stress autoantigen
- Findings foundational for understanding why immunotherapy fails in pancreatic cancer
- Endogenous retroviral and stress antigen epitopes are novel immunotherapy target classes
Implications
Understanding the natural tumor-reactive TCR repertoire could guide neoantigen vaccines and personalized T cell therapies for pancreatic cancer.
Caveats
Murine model; abstract-only. Translation to human PDAC requires validation. Most reactive T cells appear unable to control tumor growth—their diversity may not translate to immunity.
Source: Science advances — 2026-04-10
