Neutrophils in cancer drug resistance: Roles and therapeutic opportunities

The tumor microenvironment (TME) is closely associated with the therapeutic response and clinical outcome of cancer drug therapies, which mainly include immunotherapy, chemotherapy and targeted therapy. Neutrophils that infiltrate tumors, also known as tumor-associated neutrophils (TANs), constitute a primary part of the TME. However, the functional importance of TANs in cancer drug therapy has long been overlooked because of their relatively short life span. Recent studies have shown that TANs play crucial protumoral or antitumoral roles in cancer drug treatment, largely because of their diversity and plasticity. This review describes the development, heterogeneity and recruitment of neutrophils in the context of cancer and emphasizes the role and mechanisms of TANs in cancer drug resistance. Additionally, several potential neutrophil-targeted strategies are discussed.