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Furthermore, CD4+ and CD8+ T cells in the TME often exhibit functional impairment, inactivation, or exhaustion, and frequently co-express multiple immune checkpoint molecules, such as PD-1, lymphocyte activation gene 3, and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)

Thus, mTORC1 promotes the nuclear translocation of the cAMP response element-binding protein (CREB) which stimulates the transcription of the anti-apoptotic gene MCL-1 in the nucleus and the upregulation of the Bcl-2 family protein myeloid cell leukemia 1 (Mcl-1) [300]

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