Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy

Abstract

The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.

Cancer invasion and anaerobic bacteria: new insights into mechanisms

“…and F. nucleatum have also been linked with effects on immune cells and modulation of immune response to pathogens, increasing the pathogenic effects of bacteria and enabling immune cell evasion [28,[85][86][87]. Microbiota may in addition affect anticancer immunotherapy treatment, including anti-PD-L1 therapy [78], and other immunotherapies reviewed in [88,89].…”

Drug resistance mechanisms in cancers: Execution of pro-survival strategies

“…4 is one of the highly intricate processes via which cancer cells develop ways to avoid detection and destruction by the immune system, making some cancer treatments less effective. Multiple mechanisms have been demonstrated by which cancer cells avoid immune destruction including: (a) downregulation of antigen presentation [ 120 ] , (b) loss of tumor antigens [ 121 ] , (c) immune checkpoint activation [ 122 ] , (d) tumor microenvironment [ 122 ] , (e) epigenetic changes [ 123 ] , (f) tumor heterogeneity [ 124 ] , (g) influence of microbiome [ 125 ] , (h) immune escape variants; (i) immunosuppressive pathways [ 126 ] , and (j) treatment-induced changes [ 122 ] . However, discussing the details of all these mechanisms is beyond the scope of this review, and readers are directed to excellent reviews by Kim and Cho [ 122 ] and Dutta et al [ 127 ] .…”

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…It is widely accepted that dysbiotic gut microbiota plays an important role in promoting tumor cell escape from immune attack in solid tumors ( 281 – 283 ), and the response to ICI treatment is strongly influenced by the abundance and diversity of the gut microbiome ( 284 , 285 ). This also indicates that antitumor immunity necessitates the engagement of additional antigenic stimulation for immune surveillance against neoplastic antigens.…”

“…Inflammatory strength in the tumor microenvironment predicts the treatment response to ICIs ( 276 – 280 ). However, effective antitumor immunity requires additional antigen stimulation especially from the gastrointestinal tract ( 281 – 285 ), and the dynamic microbial ecosystem is the most important environmental factor for maintaining host immune homeostasis ( 146 – 148 ). Some pathogenic ( 291 – 295 ) and commensal ( 296 , 297 ) microbes can stimulate Th1 responses, enhance ICI treatment-induced antitumor immunity ( 301 – 303 ), and even directly overcome the immune exhaustion state ( 298 – 300 ).…”