Inflammation and tumor immune escape in response to DNA damage

Senescent and cancer cells share common inflammatory characteristics, including factors of the senescence-associated secretory phenotype (SASP) and the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Inflammation in the tumor microenvironment not only provides an opportunity for immune cells to attack cancer cells, but also promotes cancer invasion and metastasis. Immune checkpoint molecule PD-L1 is transcriptionally induced by inflammation, and the immunological state of PD-L1-positive tumors influences the efficacy of Immune checkpoint inhibitors (ICIs). ICIs are effective against the PD-L1-positive “hot” tumors; however, the non-immunoactive “cold” tumors that express PD-L1 rarely respond to ICIs, suggesting that converting PD-L1-positive “cold” tumors into “hot” tumors would improve the efficacy of ICIs. To eliminate cancer via the innate immune system, a therapeutic strategy for manipulating inflammatory responses must be established. To date, the molecular mechanisms of inflammation-induced tumorigenesis are not yet fully understood. However, it is becoming clear that the regulatory mechanisms of inflammation in cancer via the cGAS-STING pathway play an important role in both cancer and sensescent cells. In this review, we focus on inflammation and immune escape triggered by DNA damage in cancer and senescent cells.