Abstract
Recently, immune checkpoint inhibitors (ICIs) have demonstrated substantial benefits and potential by enhancing antitumor immune responses via the normalization of host T cell activity. Nonetheless, a considerable proportion of patients were tolerant to ICI therapy, thereby restricting its broader application in cancer treatment. Identifying the key barriers responsible for resistance to ICI therapy has led to the development of combination therapies with ICIs as a promising approach to overcome these challenges, providing new directions for ICI-based cancer immunotherapy. Neutrophils within the tumor microenvironment are considered a critical factor contributing to poor responses to ICI treatment, and combining ICIs with neutrophil-targeted therapy has shown remarkable efficacy and promise. Consequently, this review discusses the diverse roles of neutrophils in cancer immunotherapy, outlines the synergistic mechanisms of targeting neutrophils in conjunction with ICIs, highlights relevant clinical trials of this combination strategy, and discusses current limitations and future directions. Overall, this review aims to provide new insights into effective strategies for ICI therapy.