A combination treatment with a water extract from Euglena gracilis and anti-PD-1 antibody strongly inhibits growth of lung cancer in mice through stimulating tumor-infiltrating lymphocytes.

Abstract

Here, we investigated the relationship between the attenuation of lung cancer growth due to oral administration of Euglena gracilis water extract (EWE) and T cell stimulation. Orally administered EWE was revealed to increase PD-1 and PD-L1 mRNA and proteins primarily in tumor-infiltrating lymphocytes (TILs), which was correlated with a significant decrease in the tumor weights in mice. A combination treatment with EWE and anti-PD-1 antibody significantly decreased the growth of murine lung tumors more than treatment with either alone by increasing the number of TILs and attenuating T cell exhaustion. Short-chain fatty acids, which were previously shown to be increased in intestines of mice treated with oral EWE, increased both PD-1 and PD-L1 expression in splenocytes, but not in lung cancer cells in cell culture. These results suggest there is a close relationship between the EWE-induced increase of short-chain fatty acids, the increase of PD-1 expression in TILs, and the attenuation of lung tumor growth. Furthermore, EWE enhances the efficacy of anti-PD-1 antibody-based immune checkpoint blockade therapy against non-small cell lung cancer.