Integrin β7 Inhibits Colorectal Cancer Pathogenesis via Maintaining Antitumor Immunity

Abstract

Immune cell infiltration is important for predicting the clinical outcomes of colorectal cancer. Integrin b7 (ITGB7), which is expressed on the surface of leukocytes, plays an essential role in the homing of immune cells to gut-associated lymphoid tissue and facilitating the retention of lymphocytes in gut epithelium; however, its role in colorectal cancer pathogenesis is poorly explored. Here, we found that the number of b7þ cells decreased significantly in tumor tissue compared with adjacent normal tissue. b7 expression decreased in tumor-derived compared with normal tissue–derived CD8þ T cells. With bulk RNA expression data from public platforms, we demonstrated that higher ITGB7 expression correlated with longer patient survival, higher cytotoxic immune cell infiltration, lower somatic copy-number alterations, decreased mutation frequency of APC and TP53, and better response to immunotherapy. The possible cell–cell interactions mediated by ITGB7 and its ligands MAdCAM-1, VCAM-1, and CDH1 were investigated using public single-cell RNA sequencing data. ITGB7 deficiency led to exaggerated tumorigenesis and progression in both Apcmin/þ spontaneous and MC38 orthotopic models of colorectal cancer, which could be due to a reduced infiltration of activated CD8þ T cells, effector memory CD8þ T cells, IFNgþ CD8þ T cells, IFNgþ natural killer cells, CD103þ dendritic cells, and other immune cell subsets that are essential players in antitumor immunity. In conclusion, our data revealed that ITGB7 could inhibit the tumorigenesis and progression of colorectal cancer by maintaining antitumor immunity.