Tespa1 deficiency reduces the antitumour immune response by decreasing CD8⁺T cell activity in a mouse Lewis lung cancer model

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a key molecule in T-cell development and has been linked to immune diseases. However, its role in antitumour CD8⁺T cell immunity remains unclear. Here, we demonstrated that Tespa1 plays an important role in antitumour CD8⁺T cell immunity. First, compared with wild-type (WT) mice, Lewis lung cancer cells grew faster in Tespa1 knockout (Tespa1^-/-) mice, with reduced apoptosis, and decreased CD8⁺T cells in peripheral blood and tumor tissues. Second, the proportion of CD8⁺T and Th1 cells in the splenocytes of Tespa1^-/- mice was lower than that in WT mice. Third, Tespa1^-/- CD8⁺ tumor-infiltrating lymphocytes (TILs) showed weakened proliferation, invasion, cytotoxicity, and protein expression of IL-2 signalling pathway components compared to WT CD8⁺TILs. Furthermore, PD-1 expression in CD8⁺TILs was higher in Tespa1^-/- than in WT mice. Lastly, CD8⁺TILs in WT mice improved the antitumour ability of Tespa1^-/- mice. In conclusion, these findings suggest that Tespa1 plays a critical role in the tumor immune system by regulating CD8⁺T cells.

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