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Fig. 2 | Clinical and Translational Medicine

Fig. 2

From: The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies

Fig. 2

Proposed immunomodulatory mechanisms of commensal bacteria on anticancer efficacy of immune checkpoint inhibitors in animal models and patients. Oral gavage of B. fragilis in germ-free mice has been shown to induce T helper 1 (TH1) immune responses in tumor-draining lymph nodes and maturation of dendritic cells (DCs) in responders to cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade. Oral gavage of Bifidobacterium spp. in mice was shown to increase accumulation of antigen-specific CD8+ tumor-infiltrating lymphocytes (TILs) and major histocompatibility complex (MHC) Class II DCs in responders to programmed death ligand 1 (PD-L1) blockade. Human responders to programmed cell death protein 1 receptor (PD-1) blockade had significant positive correlations between CD8+ TILs or levels of CD4+ and CD8+ T-cells in the peripheral blood and abundance of select members of the Clostridiales order, Ruminococcaceae family, and Faecalibacterium genus. Oral gavage of Akkermansia muciniphila and E. hirae was associated with increased central memory CD4+ T-cells expressing the small intestine-associated chemokine receptor CCR9 and/or the TH1-associated chemokine receptor CXCR3 in mesenteric and tumor draining lymph nodes as well as increased CD4/Foxp3 ratios in tumors of mice cotreated with anti-PD-1 therapy. In human peripheral blood, secretion of cytokines by CD4+ T-cells including TH1, Tc1, and interferon-γ (IFN-γ) and bone marrow-derived DCs including IL-12 were associated with response to PD-1 blockade and reactivity against A. muciniphila and E. hirae (for Tc1)

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