Background: CD8⁺ T cells play a crucial role in immune responses, and have significant potential in tumor immunotherapy. The JAK/STAT pathway is essential for cytokine signal transduction and is linked to immune escape. However, its role in mediating CD8⁺ T cell anti-tumor immunity in renal cancer is not fully understood.
Objective: To study the mechanisms underlying CD8⁺ T cell-mediated anti-tumor immunity and propose new possibilities for immunotherapy in patients with renal cancer.
Methods: CD8⁺ T cells from mouse spleens were sorted using immunomagnetic beads, and their purity was confirmed by flow cytometry. Proliferation was analyzed using CCK-8 and CFSE assays. Activation of CD8⁺ T cells was assessed through ELISA and Western blotting. The malignant properties of Renca cells were evaluated through flow cytometry, Calcein-AM/PI staining, wound healing, Transwell, Western blot, and immunofluorescence. A subcutaneous tumor model in nude mice was used to examine the role of JAK1/STAT1 pathway in vivo.
Results: Inhibitors of JAK1 and STAT1 significantly reduced the proliferation and activation of CD8⁺ T cell. Co-culture with CD8⁺ T cells increased apoptosis and inhibited the proliferation, migration, and invasion of Renca cells. The effects were diminished by JAK1 and STAT1 inhibitors, confirming that CD8⁺ T cells exert antitumor effects through the JAK1/STAT1 pathway. In vivo, inhibition of this pathway reduced the anti-tumor effects of CD8⁺ T cells.
Conclusion: Inhibitors of JAK1 and STAT1 weakened the antitumor effects of CD8⁺ T cells, suggesting that targeting this pathway could enhance CD8⁺ T cell-mediated immunity in renal cancer.