Abstract:
Objective This study explored the relationship between Vav1 and tumor-infiltrating T lymphocytes (TIL - T), which provide a molecular mechanism inducing a state of T cell anergy. The expression of Vav1 in TIL-T and indoleamine 2, 3-dioxygenase (IDO) from the tumor microenvironment was invetigated in order to present a possible molecular mechanism for tumor-induced T cell immune tolerance.
Methods A total of 40 lung cancer patients who had undergone surgery in the Tianjin Medical University Cancer Institute and Hospital were involved. The expression levels of Vav1 mRNA in TIL-T were detected by real-time PCR, while the expression and activation of Vav1 were determined using Western blot and immunoprecipitation. T cell proliferation was detected using the BrdU method. The levels of IDO expression in lung cancer and corresponding normal lung tissues were determined using semi-quantitative RT-PCR, immunohistochemistry, and Western blot. The SPSS17.0 software was used for statistical analysis.
Results TIL-Ts are a part of cancer tissues and are in a state of functional suppression. This suppressive condition may involve the key signal transducer Vav1. Both mRNA and protein levels of Vav1 in T cells were significantly decreased in lung cancer tissues with IDO-positive expression compared with those with IDO-negative expression. In addition, the levels of Vav1 phosphorylation was decreased (P < 0.05).
Conclusion The expression and activation of Vav1 play critical roles in the function of TIL-T. IDO, secreted by the tumor cells themselves or antigen-presenting cells, has an important impact on the expression and activation of Vav1 in TIL-T. IDO may suppress the expression and phosphorylation of Vav1, leading to inhibition of the T cell active immune response, which may consequently reduce the anti-tumor defenses of the host.
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