Effects of Gut Microbiota on Host Adaptive Immunity Under Immune Homeostasis and Tumor Pathology State

Abstract

Gut microbiota stimulate and shape the body's adaptive immune response through bacterial components and its active metabolites, which orchestrates the formation and maintenance of the body's immune homeostasis. In addition, the imbalances in microbiota-adaptive immunity contribute to the development of tumor and the antitumor efficiency of a series of antitumor therapies at the preclinical and clinical levels. Regardless of significant results, the regulation of gut microbiota on adaptive immunity in immune homeostasis and tumors needs a more thorough understanding. Herein, we highlighted the comprehensive knowledge, status, and limitations in the mechanism of microbiome interaction with adaptive immunity and put forward the prospect of how to translate these insights in inhibiting tumor progression and enhancing the efficacy of antitumor interventions.

Keywords: adaptive immunity; homeostasis; immunotherapy; microbiota; tumor.

Figure 1

Gut microbiota affects adaptive immunity under physiological conditions through a series of immune signal. 1. Muciniphila can stimulate TH0 cells to differentiate into TfH cells. 2–6. Symbiotic bacteria promote Th17 differentiation through a series of immune signal mediations. 7. The metabolites of bacteria, 3-oxolithocholic acid (secondary BA) inhibit Th17 cell differentiation. 8–11. Flagellin of symbiotic bacteria, symbiotic bacteria, and their metabolites can promote Th1 differentiation. 12–19. The differentiation of Treg can be induced by symbiotic bacteria, their mixture and metabolites. 20. Butyrate can enhance the memory effect of CD8+ T cells. 21. Increased acetic acid concentration is integrated by CD8+ T cell function, promoting rapid memory CD8+ T cell response. 22. SCFA treated with CD4+ T cells as an HDAC inhibitor can upregulate expression of CTL gene and increase CD4+ T cells.

Figure 2

The tumor environment was profoundly altered by gut microbiota which could influence a series of antitumor therapies such as antigen mimic of microbiota, chemotherapy, ICB immunotherapy, and radiotherapy through adaptive immune approach. The specific microbiota could enhance the activation of DCs, increase the infiltration of CTLs, and decrease the Tregs in TME, which significantly sensitize these therapies.