Good cops turn bad: The contribution of neutrophils to immune-checkpoint inhibitor treatment failures in cancer

Abstract

Immune checkpoint inhibitor therapy activates tumor-killing T-cells by releasing the brake of anti-tumor immunity. It has been approved as first- or second-line therapy in many cancer types. Unfortunately, a majority of immune checkpoint inhibitor recipients are refractory to the therapy. Recent investigations of the peripheral blood and tumor microenvironment of cancer patients indicate that high neutrophil content is associated with poor response rates, suggesting an opportunity for synergistic therapy. In the current review, we discuss the mechanisms of neutrophil-mediated immunosuppression in cancer and recent findings suggesting that neutrophil antagonism will improve the efficacy of immune checkpoint inhibitor therapy.

Keywords: Immune checkpoint inhibitor; Neutrophil; PMN-MDSC; TME.