Bojungikki-Tang enhances the effect of PD-1 blockade in a murine model of lung carcinoma

Abstract Although immunotherapy is effective against non-small cell lung cancer (NSCLC), only a limited number of patients benefit from it clinically. Resistance to immunotherapeutic agents hinders effective treatment. Of late, the usefulness of herbal medicines in combination with immunotherapy is being investigated. Bojungikki-Tang (BJIKT) is a widely used traditional herbal medicine, but its antitumor effect with immunotherapy in NSCLC are unclear. Thus, in this study, we investigated the combined effects of BJIKT and anti-PD-1 antibody in a KLN205-DBA/2 syngeneic lung cancer model. Immunohistochemistry and flow cytometry analyses were performed to analyze the changes in immune cells in the tumor microenvironment. BJIKT plus anti-PD-1 antibody significantly inhibited tumor growth unlike the respective monotherapies. The combination treatment increased the population of CD8 + cytotoxic T cells and decreased the number of Ki67 + cells in the tumor tissues compared to that observed with monotherapy. The combination treatment decreased the proportion of myeloid-derived suppressor cells, but increased the proportion of M2-like macrophages, compared to that observed with monotherapy. Cytokine analysis showed that the combination treatment increased the levels of T helper type 1-related cytokines, including IFN-γ and TNF-α. Network pharmacology analysis revealed that BJIKT might regulate immune functions related to NSCLC progression. These findings indicate that combination treatment with BJIKT and anti-PD-1 antibody effectively suppresses tumor growth by regulating immune function, and may be an alternative therapeutic option for the treatment of NSCLC.