Genetic alterations shape innate immune cells to foster immunosuppression and cancer immunotherapy resistance.

Cancer immunotherapy, particularly immune checkpoint inhibitors, has opened a new avenue for cancer treatment following the durable clinical benefits. Despite the clinical successes across several cancer types, primary or acquired resistance might eventually lead to cancer progression in patients with clinical responses. Hence, to broaden the clinical applicability of these treatments, a detailed understanding of the mechanisms limiting the efficacy of cancer immunotherapy is needed. Evidence provided thus far has implicated immunosuppressive innate immune cells infiltrating the tumor microenvironment as key players in immunotherapy resistance. According to the available data, genetic alterations can shape the innate immune response to promote immunotherapy resistance and tumor progression. Herein, this review has discussed the current understanding of the underlying mechanisms where genetic alterations modulate the innate immune milieu to drive immunosuppression and immunotherapy resistance.