Fig. 2
From: Prospects for combining immune checkpoint blockade with PARP inhibition
The cross-talk between DNA damage and immune response. Following the stimulation of cytoplasmic dsDNA, cGAS is activated and catalyzes the generation of cyclic-dinucleotide. CDN is a second messenger which promotes the conformational change of STING. Active STING mainly initiates the downstream TBK1-IRF3-Type I IFN pathway. Besides, STING could activate the NF-κB pathway which cooperates with IRF3 to upregulate the generation of type I IFN. Type I IFN has a substantial influence on systemic immune response and regulates multiple components in anti-cancer immunity. Moreover, PARPi treatment-induced double-strand break could upregulate PD-L1 expression by augmented anti-cancer immunity or ATM-ATR-Chk1 pathway. Lastly, after receiving PARPi treatment, accumulated chromosome rearrangements generate plenty of neoantigens and elevate the immunogenicity of tumor. DSB, double-strand break; STING, stimulator of interferon genes; cGAS cyclic GMP-AMP synthase; TMB, tumor mutation burden