Gut microbiota and dietary intervention: affecting immunotherapy efficacy in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. In recent years, treatment with immune checkpoint inhibitors (ICIs) has gradually improved the survival rate of patients with NSCLC, especially those in the advanced stages. ICIs can block the tolerance pathways that are overexpressed by tumor cells and maintain the protective activity of immune system components against cancer cells. Emerging clinical evidence suggests that gut microbiota may modulate responses to ICIs treatment, possibly holding a key role in tumor immune surveillance and the efficacy of ICIs. Studies have also shown that diet can influence the abundance of gut microbiota in humans, therefore, dietary interventions and the adjustment of the gut microbiota is a novel and promising treatment strategy for adjunctive cancer therapy. This review comprehensively summarizes the effects of gut microbiota, antibiotics (ATBs), and dietary intervention on the efficacy of immunotherapy in NSCLC, with the aim of informing the development of novel strategies in NSCLC immunotherapy.

Keywords: PD-1/PD-L1; antibiotics; dietary intervention; gut microbiota; non-small cell lung cancer.

Figure 1

Dietary intervention and gut microbiota regulate the efficacy of immunotherapy for NSCLC. Dietary interventions and antibiotics can influence the efficacy of anti-PD-1/PD-L1 treatment by influencing the abundance of gut microbiota—which includes the synergistic and antagonistic effect of microbiota on PD-1/PD-L1 therapy—by modulating innate and/or adaptive immunity. NSCLC, Non–small Cell Lung Cancer; PD-L1, Programmed cell death ligand 1; PD-1, Programmed cell death 1.

Figure 2

A variety of gut microbiota can affect the efficacy of immunotherapy for NSCLC through multiple immune mechanisms, such as Bifidobacteria, Bifidobacterium longum, Bifidobacterium breve, LGG, AKK, Enterococcus bacteriophage, Nissle 1917. AKK, Akkermansia muciniphila; LGG, Lactobacillus rhamnosus GG; TNFα, tumor necrosis factor alpha; KbSIY, a model neoantigen, SIYRYYGL; CRISPR/Cas9, clustered regularly interspaced short palindromic repeat; ROS, reactive oxygen species; ICD, immunogenic cell death; IDO1, indolea-mine 2,3-dioxygenase-1; TMP1, the epitope-tail length measurement protein 1; PSMβ-4, proteasome subunit beta-4.

Figure 3

The effect of dietary interventions for the treatment of NSCLC immune. a. GPs increases the antitumor response to anti-PD-1 antibodies by regulating bacteria such as Muribaculum. b. RESV can improve the tumor immunosuppressive microenvironment through multiple mechanisms and promote immune cell-mediated immunotherapy response. c. Castalagin increases the anti-tumor response of anti-PD-1 antibodies by modulating bacteria such as Ruminococcus. d. SFRE combined with pembrolizumab enhanced the anti-PD-L1 immune response of tumor cells and improved the efficacy of immunotherapy. e. SV improves the immunosuppressive microenvironment of tumors by promoting multiple immune response pathways. f. Dietary intervention combined with immunotherapy improves immunotherapy efficacy and prolongs overall survival in patients with NSCLC. GPs, Ginseng polysaccharides; RESV, Resveratrol; SFRE, Supercritical extraction of rosemary; SV, Specific vegetable extracts.