Cancer therapy using
immune checkpoint inhibitors (ICIs) is a promising clinical strategy for patients with multiple types of
cancer. The expression of programmed cell death ligand-1 (PD-L1), an immune-suppressor
ligand, in
cancer cells is
a factor that influences the efficacy of ICI
therapy, particularly in the anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody
therapy. PD-L1 expression in
cancer cells are associated with
tumor mutation burden including
microsatellite instability because the accumulation of mutations in the
cancer genome can produce abnormal
proteins via mutant mRNAs, resulting in neoantigen production and HLA-neoantigen complex presentation in
cancer cells. HLA-neoantigen presentation promotes immune activity within
tumor environment; therefore, known as hot
tumor. Thus, as the fidelity of DNA repair affects the generation of genomic mutations, the status of DNA repair and signaling in
cancer cells can be considered prior to ICI
therapy. The
Cancer Genome Atlas (TCGA) and The
Cancer Immunome Atlas (TCIA) database analysis showed that
tumor samples harboring mutations in any non-homologous end joining, homologous recombination, or DNA damage signaling genes exhibit high neoantigen levels. Alternatively, an urgent task is to understand how the DNA damage-associated
cancer treatments change the status of immune activity in patients because multiple clinical trials on combination
therapy are ongoing. Recent studies demonstrated that multiple pathways regulate PD-L1 expression in
cancer cells. Here, we summarize the regulation of the immune response to ICI
therapy, including PD-L1 expression, and also discuss the potential strategies to improve the efficacy of ICI
therapy for poor responders from the viewpoint of DNA damage response before or after DNA damage-associated
cancer treatment.