Mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade and the emerging role of gut microbiome

Acquired resistance for immune checkpoint inhibitors in cancer immunotherapy: challenges and prospects

“…By using bacterial ablation, the TME can be remodeled, which is characterized by the reduction of MDSCs, the differentiation of M1 macrophages and CD4+ T cells, and the activation of CD8+ T cells. In addition, probiotics can inhibit the proliferation of tumor cells by regulating intestinal microbiota, such as by promoting the growth of shortchain fatty acid (SCFA)-producing bacteria [109].…”

The role of gut microbiome in immune modulation in metastatic renal cell carcinoma

“…Perhaps more critical than molecular mimicry is the microbiota’s critical role in modulating immune response by producing metabolites that induce immune responses or promote the development of anti-TMEs. 12 , 19 Of the metabolites produced, short-chain fatty acids (SCFAs) such as butyrate and propionate have been implicated in anti-tumor activity in colorectal cancer. 12 SCFAs have been found to inhibit transcription factors involved in tumorigenesis by inhibiting histone deacetylase and can indirectly regulate tumor development by modulating inflammation.…”

“…Some of the metabolites can regulate the permeability of the intestinal wall as a form of protection against carcinogens and by regulating homeostasis among pro- and anti-inflammatory immune cytokines. 19 The gut microbes interact with the host immune system by inducing T-cell responses by their antigens and their metabolism and production of small molecules that regulate the cell microenvironment. 19 For example, Bacteroides fragilis is involved in the differentiation of CD4 + cells into regulatory T cells and secrete cytokines such as interleukin (IL)-10.…”

“… 19 The gut microbes interact with the host immune system by inducing T-cell responses by their antigens and their metabolism and production of small molecules that regulate the cell microenvironment. 19 For example, Bacteroides fragilis is involved in the differentiation of CD4 + cells into regulatory T cells and secrete cytokines such as interleukin (IL)-10. 23 The increased cytokines may also enhance the autoimmune effects of ICIs.…”

“…Bacteroides species have also been associated with augmented response to anti-CTLA-4 therapy in melanoma. 19 , 23 Bacteroides species are known to produce capsular polysaccharides that induce adaptive T-cell-mediated immune responses. 66 Bifidobacterium spp.…”