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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
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
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
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
  1. MC38 colon carcinoma, B16 melanoma, ODN oligodeoxynucleotides, IT intratumoral, IP intraperitoneal, IL-10 interleukin-10, Abs antibodies, TNF tumor necrosis factor, spp. species, MCA205 sarcoma, Ret melanoma, B16.SIY melanoma, CTLA-4 cytotoxic T-lymphocyte associated protein 4, B16.SIY melanoma, MB49 bladder cancer, PD-L1 programmed death ligand 1, LLC Lewis lung carcinoma, PD-1 programmed cell death protein 1, B16.SIY melanoma, R responder, NR nonresponder