Immune cell infiltration is closely related with tumor initiation, progression and prognosis. Integrin β7, 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. β7 has been reported to inhibit the development of colitis, however its role in the pathogenesis of colorectal cancer (CRC) is still unclear.
In a recent study published in Cancer Immunology Research on June 15, 2021, a research team led by CHEN Jianfeng from CAS Center for Excellence in Molecular Cell Science/Shanghai Institute of Biochemistry and Cell Biology, LI Jiyu and WEI Qing from Shanghai Tenth People's Hospital, demonstrated that integrin β7 inhibits colorectal cancer pathogenesis via maintaining anti-tumor immunity.
In the present study, the researchers found that the number of β7+ immune cells decreased significantly in tumor tissue compared with adjacent normal tissue. β7 expression decreased in tumor-derived compared to normal tissue-derived CD8+ T cells. Higher β7 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. Finally, they found that β7 deficiency led to exaggerated tumorigenesis and progression in both Apcmin/+ spontaneous and MC38 orthotopic models of CRC, which could be due to a reduced infiltration of activated CD8+ T cells, effector memory CD8+ T cells, IFNγ+ CD8+ T cells, and other immune cell subsets that are essential players in anti-tumor immunity.