Research Progress of Metabolites of Intestinal Microbiota Reshaping Tumor Immune Microenvironment and Immunotherapy Response Through PD-1/PD-L1 Pathway

School of Life Science, Shanxi Normal University, 030031 Taiyuan City, Shanxi Province, China

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Abstract

Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) are a key clinical approach for treating cancer. Recently, many researchs have uncovered that the intestinal flora and its metabolites can modulate immune regulation, thereby influencing the tumor microenvironment and taking on a crucial role in determining treatment efficacy. This review mainly focuses on the effects of gut microbiota metabolites on the PD-1/PD-L1 pathway and immune regulatory mechanisms, exploring receptor-dependent signaling pathways and epigenetic programming mechanisms underlying immune therapy in various tumors; the impact of these mechanisms on the transformation of the tumor microenvironment between “immunologically cold” and “immunologically hot” states; the causal chain linking microbiota metabolites, immunity, tumor microenvironment; the dual effects of gut microbiota-derived metabolites on promoting or inhibiting immune checkpoints; fecal microbiota transplantation (FMT) acts as a strategy in reshaping the gut microbiota. Finally, it outlines future prospects and challenges, aiming to deepen the understanding of host-microbiota–tumor microenvironment crosstalk and to enhance the clinical efficacy of combination therapies.