Impact of DNA Damage Response—Targeted Therapies on the Immune Response to Tumours

SIMPLE SUMMARY: Targeting tumour-specific defects in the DNA damage response (DDR) presents an opportunity for new therapeutic approaches to selectively kill cancer cells. Although the therapeutic rationale of DDR-targeted agents initially focused on their actions against tumour cells, these agents might also alter the crosstalk between tumour cells and the immune system. Here, we discuss recent data showing that DDR-targeted agents affect the antitumour immune response both through direct actions on the immune system components and through indirect effects on expression of different molecules and pathways in tumour cells that underpin the tumour cell–immune system. ABSTRACT: The DNA damage response (DDR) maintains the stability of a genome faced with genotoxic insults (exogenous or endogenous), and aberrations of the DDR are a hallmark of cancer cells. These cancer-specific DDR defects present new therapeutic opportunities, and different compounds that inhibit key components of DDR have been approved for clinical use or are in various stages of clinical trials. Although the therapeutic rationale of these DDR-targeted agents initially focused on their action against tumour cells themselves, these agents might also impact the crosstalk between tumour cells and the immune system, which can facilitate or impede tumour progression. In this review, we summarise recent data on how DDR-targeted agents can affect the interactions between tumour cells and the components of the immune system, both by acting directly on the immune cells themselves and by altering the expression of different molecules and pathways in tumour cells that are critical for their relationship with the immune system. Obtaining an in-depth understanding of the mechanisms behind how DDR-targeted therapies affect the immune system, and their crosstalk with tumour cells, may provide invaluable clues for the rational development of new therapeutic strategies in cancer.