The role of rhamnose derived from gut microbiome in modulating the efficacy of non-small cell lung cancer immunotherapy.

Abstract

e14586 Background: In recent years, the relationship between gut microbiota and metabolites and immunotherapy for non-small cell lung cancer （NSCLC） has gradually become a research hotspot. Rhamnose is a monosaccharide that can be secreted by the gut microbiome and has certain potential in regulating immune responses. The mechanism by which Rhamnose regulates the efficacy of immunotherapy for NSCLC is not yet clear. The aim of this study is to explore the mechanism by which gut microbiome metabolite rhamnose regulates the efficacy of immunotherapy for non-small cell lung cancer, providing new ideas for improving the efficacy of immunotherapy for non-small cell lung cancer. Methods: According to the progression free survival (PFS) of NSCLC patients after immunotherapy, they were divided into a response group (PFS > 6 months, R group) and a non-response group (PFS ≤ 6 months, NR group). Baseline fecal samples were collected from patients for non-targeted metabolomics sequencing to screen for rhamnose. Using a mouse lung cancer model, mice were divided into a control group, a rhamnose group, an anti-PD-1 treatment group, and a combination therapy group (rhamnose +anti-PD-1). Observe the changes in tumor volume in different groups of mice. Flow cytometry and immunohistochemical were used to detect changes in tumor infiltrating CD8 + T cells in different groups of mice. ELISA was used to detect the expression levels of IFN - γ and Granzyme B in the plasma of different groups of mice. Results: Non-targeted metabolomics sequencing found that compared with the NR group, the R group had significantly increased levels of rhamnose. In vivo studies on mice showed that compared to the anti-PD-1 monotherapy group, the combination treatment group showed a significant slowdown in tumor volume growth. The results of flow cytometry and immunohistochemical showed that compared with the anti-PD-1 monotherapy group, the infiltration of CD8 + T cells in tumor tissues increased in the combination treatment group. According to the ELISA results, the proportion of IFN - γ and Granzyme B in peripheral blood of the combined treatment group also increased, indicating the regulatory effect of rhamnose on systemic immune response. Conclusions: The efficacy of NSCLC immunotherapy may be related to gut microbiome metabolite rhamnose. Rhamnose enhances the function of CD8 + T cells by increasing tumor infiltration and raising the levels of cytokine IFN–γ and Granzyme B.