JAK/STAT Signaling Pathway Mediates Anti-Tumor Immunity of CD8+ T Cells in Renal Cancer

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.