Abstract
Tumor-infiltrating immune/inflammatory cells, the important components of the tumor microenvironment (TME), remarkably affect the progression of human cancers. To understand the actual conditions within the TME of colorectal cancer (CRC), the interrelationship among tumor-infiltrating neutrophils, M2 macrophages, and regulatory T-cells (Tregs) was systematically analyzed. The infiltration conditions of CD66b+ neutrophils, CD163+ M2 macrophages, and FOXP3+ Tregs in tissue microarrays including 1021 cases of CRC were determined by immunohistochemical analysis. The prediction power of these immune cells for CRC prognosis was evaluated by subgroup analysis of the CRC cohort. Results revealed the existence pattern of infiltrating neutrophils, and Tregs/M2 macrophages fulfilled a "X-low implies Y-high" Boolean relationship, indicative of a mutually exclusive correlation between neutrophils and M2 macrophages, and between neutrophils and Tregs in the TME of CRC. What's more, the tumor-infiltrating M2 macrophages and Tregs were associated with adverse prognostic factors, whereas neutrophils were corelated with favorable factors. The high infiltration of neutrophils predicted longer survival and better chemotherapeutic response. Nonetheless, high infiltration of M2 macrophages and Tregs predicted poor prognosis. The combination of these tumor-infiltrating immune cells can serve as an effective predictor for the survival of CRC and for the chemotherapeutic outcomes of stage II-III patients. .