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Combinatorial immunotherapy drives exhaustion in tumor antigen-specific CD8+ T cells within the mouse renal tumor microenvironment - PubMed

3 hours ago
  • #immunotherapy
  • #renal cancer
  • #CD8+ T cells
  • Combinatorial immunotherapy (anti-PD-1 + anti-VEGFR-2) was tested in a mouse renal cancer model.
  • A novel model was developed to track tumor antigen-specific (TAS) CD8+ T cells in renal tumors.
  • Renca-tERK-LUC tumor cells were engineered to express a model antigen (tERK) recognized by transgenic CD8+ T cells.
  • Therapy responders showed increased frequencies of activated and exhausted CD8+ TILs, activated CD4+ TILs, and NK cells.
  • TAS CD8+ TILs exhibited reduced phenotypic heterogeneity and higher PD-1+CD39+CD44+ expression compared to endogenous CD8+ TILs.
  • The model may help understand TAS CD8+ TIL biology and improve immunotherapies for renal cell carcinoma (RCC).