Table 1 Published preclinical studies investigating the relationship between gut microbiota and antitumor efficacy of immunotherapy
From: The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies
Model | Microbial intervention | Immunotherapy | Findings | References |
|---|---|---|---|---|
MC38 and B16 tumor-bearing mice | Vancomycin, imipenem/cilastatin, neomycin in drinking water Oral gavage | IT CpG-ODN and IP anti-IL-10 Abs | Impaired TNF-dependent antitumor activity and worse survival in antibiotic-treated and germ-free mice Number of Allstipes and Ruminococcus spp. positively correlated while Lactobacillus spp. negatively correlated with TNF-dependent tumor response to immunotherapy | [16] |
MCA205, Ret, and MC38 tumor-bearing mice | Ampicillin, colistin, and streptomycin or imipenem Oral gavage Fecal transplantation | IP anti-CTLA-4 Ab | Impaired antitumor activity in germ-free or antibiotic-treated mice but not in specific pathogen-free mice In antibiotic-treated mice, oral feeding with Bacteroides fragilis, Bacteroides thetaiotaomicron, or Burkholderia cepacia recovered anti-CTLA-4 response In germ-free mice, oral feeding with Bacteroides fragilis recovered anti-CTLA-4 response Abundance of Bacteroides spp. (not B. distasonis or B. uniformis) correlated with response in human to mice fecal transplantation studies | [17] |
B16.SIY and MB49 tumor-bearing mice | Oral gavage | IP anti-PD-L1 Ab | Bifidobacterium spp.-treated mice had significantly improved tumor control vs. non-Bifidobacterium-treated mice | [18] |
BP tumor-bearing mice | Fecal transplantation | IP anti-PD-L1 Ab | Responders had significantly higher abundance of Faecalibacterium spp. and Ruminococcaceae family, while nonresponders had higher abundance of Bacteroidales order | [19] |
MCA205, LLC, and Ret tumor-bearing mice | Ampicillin, colistin, and streptomycin Fecal transplantation Oral gavage | IP anti-PD-1 Ab ± anti-CTLA-4 Ab | Worse survival in antibiotic-treated and specific pathogen-free mice Reconstitution with Akkermansia muciniphila ± Enterococcus hirae or Alistipes indistinctus reversed resistance to PD-1 blockade in antibiotic-treated mice | [20] |
B16.SIY tumor-bearing mice | Fecal transplantation | IP anti-PD-L1 Ab | 2/3 mouse cohorts reconstituted with R fecal material showed slower baseline tumor growth 2/3 mouse cohorts reconstituted with NR fecal material showed faster baseline tumor growth Anti-PD-L1 efficacy seen in mice colonized with R microbiota vs. completely ineffective in NR-derived mice | [21] |