Abstract
Negative immune checkpoint blockade immunotherapy has shown potential for multiple malignancies including colorectal cancer (CRC). B7-H5, a novel negative immune checkpoint regulator, is highly expressed in tumor tissues and promotes tumor immune escape. However, the clinical significance of B7-H5 expression in CRC and the role of B7-H5 in the tumor microenvironment (TME) has not been fully clarified. In this study, we observed that high B7-H5 expression in CRC tissues was significantly correlated with the lymph node involvement, AJCC stage, and survival of CRC patients. A significant inverse correlation was also observed between B7-H5 expression and CD8+ T-cell infiltration in CRC tissues. Kaplan−Meier analysis showed that patients with high B7-H5 expression and low CD8+ T-cell infiltration had the worst prognosis in our cohort of CRC patients. Remarkably, both high B7-H5 expression and low CD8+ T infiltration were risk factors for overall survival. Additionally, B7-H5 blockade using a B7-H5 monoclonal antibody (B7-H5 mAb) effectively suppressed the growth of MC38 colon cancer tumors by enhancing the infiltration and Granzyme B production of CD8+ T cells. Importantly, the depletion of CD8+ T cells obviously abolished the antitumor effect of B7-H5 blockade in the MC38 tumors. In sum, our findings suggest that B7-H5 may be a valuably prognostic marker for CRC and a potential target for CRC immunotherapy.
Highlights
Colorectal cancer (CRC) is a common malignant gastrointestinal tumor that seriously threatens human life and health [1]
The results noted that B7-H5 expression was significantly correlated with the lymph node involvement (P = 0.036), AJCC stage (P = 0.037), and survival (P = 0.026)
It has been previously reported that the aberrant expression of B7H5 in cancers is related to the poor prognosis for multiple cancers, such as lung cancer, oral squamous cell carcinoma, and CRC [20]
Summary
Colorectal cancer (CRC) is a common malignant gastrointestinal tumor that seriously threatens human life and health [1]. Its morbidity and fatality rates have been on the rise in recent years. The global incidence and the mortality rate of CRC ranked third and second among all malignant tumors according to the statistics in 2020 [2]. The incidence of CRC is increasing in China, especially in cities. Some traditional cancer treatments, such as surgery, chemotherapy, and radiation therapy, have been proven to prolong the 5-year life span of CRC patients, but these aforementioned treatments are still not ideal for CRC patients with advanced stages [3]. It is extremely urgent to develop effective treatments for CRC patients and reduce the social burden caused by such diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
