Tumor-Associated Neutrophils in Colorectal Cancer Development, Progression and Immunotherapy

SIMPLE SUMMARY: Tumor-associated neutrophils (TANs) may differentiate into different patterns under the stimulation of different factors, and they play a dual role in the occurrence and progression of tumors in direct or indirect ways. The existing immune checkpoint inhibitors (ICIs) are effective in a small number of microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) colorectal cancer (CRC) patients, but they are still not suitable for microsatellite-stability (MSS) CRC patients. As an important component of the tumor immune microenvironment, TANs may overturn the current situation of immunotherapy for CRC. This review systematically summarizes the key regulatory role of TANs in the carcinogenesis, proliferation and metastasis of CRC, the prognostic value of TANs for CRC patients and the new immunotherapy strategies based on TANs as a target, providing an important reference for TANs as new target for CRC immunotherapy. ABSTRACT: The colorectal-cancer (CRC) incidence rate and mortality have remained high for several years. In recent years, immune-checkpoint-inhibitor (ICI) therapy has rapidly developed. However, it is only effective in a few CRC patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) CRC. How to improve the efficiency of ICI therapy in CRC patients with microsatellite stability (MSS) remains a huge obstacle. Tumor-associated neutrophils (TANs), which are similar to macrophages, also have N(1) and N(2) phenotypes. They can be recruited and polarized through different cytokines or chemokines, and then play an antitumor or tumor-promoting role. In CRC, we find that the prognostic significance of TANs is still controversial. In this review, we describe the antitumor regulation of TANs, and their mechanism of promoting tumor progression by boosting the transformation of inflammation into tumors, facilitating tumor-cell proliferation, metastasis and angiogenesis. The targeting of TANs combined with ICIs may be a new treatment model for CRC. Relevant animal experiments have shown good responses, and clinical trials have also been carried out in succession. TANs, as “assistants” of ICI treatment, may become the key to the success of CRC immunotherapy, although no significant results have been obtained.