Fig. 6.

Critical genes and signalling pathways engage in T cell anti-tumour responses. CRISPR screens results have revealed several intriguing genes and pathways that could potentially illuminate ways to enhance T cell functions in cancer immunotherapies. 1) JAK/STAT signalling pathway is essential in various cytokine production and transcription factors generation. Different interleukins and interferons mediate different biological function in T cell effector functions and fate determination. 2) NF-κB signalling pathway is indispensable for TCR signal transduction, and is correlated with enhanced T cell effector function and resistance to exhaustion. 3) BATF is an important AP-1 family transcription factor that functionally cooperates with IRF4 to regulate T cell proliferation, survival, and cytotoxicity. Critical T cell functional transcription factors including T-bet, Runx3, and Blimp-1 are also BATF-dependent. The role of BATF in T cell exhaustion remains unclear. Blimp-1 is highly expressed in exhausted T cells. Blimp-1 deficiency in CD8⁺ T cells indicates a higher possibility of memory cells and lower effector or exhausted phenotypes. TOX is a nuclear factor that maintains CD4⁺ and CD8⁺ T cell development, but leads to exhausted T cell phenotypes. Deletion of TOX in CD8⁺ T cells reverses the exhaustion markers expression, but fails to rescue the impaired effector function against tumours