The cytotoxicity of T cells in non-small cell lung cancer mediated via coordination of the BCL-2 and AKT pathways.

The effectiveness and mechanisms of T-cell immunotherapy in lung cancer remain unclear. In this study, we assessed the effects of continuous, low-dose T-cell intervention on lung cancer cells. We cultured T cells with a lung cancer cell line (A549) and replaced the T-cell population every 48 hours. The killing effect of Tcells on A549 cells and the Half-maximal inhibitory concentration (IC50) value were detected by the cholecystokinin octapeptide (CCK-8) method. The levels of perforin, granzyme B and the inflammatory factors interleukin-6 (IL-6), interferon (IFN)-γ, and tumor necrosis factor-alpha (TNF-a), in the supernatants of cocultured cells were measured by ELISA. The protein expression of Bcl-2, Bax, PI3K and Akt was detected by western blotting. Our results indicated that T-cell treatment decreased the protein expression of Bcl-2, PI3K, and AKT but upregulated that of Bax. Moreover, T-cell treatment increased perforin and granzyme B release related to the Bax/Bcl-2 signaling pathway. In addition, T-cell-mediated cytolysis for A549 cells involved the PI3K/AKT pathway. In vivo results were consistent with the in vitro results. T-cell immunotherapy integrated regulation of a signaling pathway network involving the mutual regulation of apoptosis and proliferation. T-cell immunotherapy could be used to enhance the cytotoxic killing of lung cancer cells.