Table 3.
Studies on improving the effect of antitumor immunotherapy by probiotics
| Tumor type | Immunotherapy treatment | Species/strain | Overview of mechanism | References |
|---|---|---|---|---|
| CRC (AOM-DSS/MC38); bladder cancer (MB49); melanoma (B16-F10) | αCTLA-4 mAb | Bifidobacterium pseudomonas | Inosine produced by the gut microbiota can translocate to the tumor microenvironment and activated T cells by adenosine A2A receptor combined with costimulation of CpG and IL-12 released by DCs for Th1 differentiation, which results in IFN-γ production and enhanced ICB therapy | [134] |
| Sarcoma (MCA205); RET melanoma; Lewis lung cancer (LLC) | αPD-1 mAb; αCTLA-4 mAb combined with αPD-1 mAb | Akkermansia muciniphila | Oral supplementation with Akkermansia muciniphila restored the efficacy of ICB in an il-12-dependent manner by increasing the recruitment of CCR9+ CXCR3+ CD4+ T lymphocytes into tumor beds | [17] |
| CRC (MC38); Lewis lung cancer (LLC1); breast cancer (4T1) | Oxaliplatin; αPD-1 mAb | Bifidobacterium bifidum | Peptidoglycan expressed at high levels in Bifidobacterim bifidum can act as TLR2 receptor to stimulate IFN-γ secretion and improve antitumor therapy by αPD-1 mAb or oxaliplatin | [127] |
| CRC (MC38); melanoma (BrafV600E Pten−/−) | αCTLA-4 mAb; αPD-1 mAb | A mixture of 11 strains (11-mix) | An 11-strain mix induces the accumulation of IFN-γ+ CD8+ T cells through the effects of CD103+ DCs in the colonic lamina propria in an MHC Ia dependent manner, thereby activating the antitumor immune response | [187] |
| Colon cancer | αCTLA-4 mAb | Lactobacillus acidophilus | Lysates of Lactobacillus acidophilus reduced the number of Treg and M2 cells in tumor-draining lymph nodes and mesenteric lymph nodes, increased the ratio of memory CD8+ T cells, and promoted an antitumor immune response | [147] |
| Melanoma (B16.SIY/B16.F10) bladder cancer (MB49) | αPD-1 mAb | Bifidobacterium breve and Bifidobacterium longum mixtures | Bifidobacterium-derived signals enhanced the effector function of tumor-specific CD8+ T cells and promoted an antitumor immune response by modulating DC activation | [190] |
| Sarcoma (MCA205); RET melanoma; metastatic melanoma; CRC (MC38/CT26) | αCTLA-4 mAb | Bacteroides fragilis | The capsular polysaccharides of Bacteroides thetaiotaomicron and Bacteroides fragilis induce the maturation of lamina propria DCs, combined with the Th1 immune response induced by IL-12 secretion, and promotes the antitumor effect of αCTLA-4 mAb | [71] |
| Lewis lung cancer (LLC) | Cis-platinum | Akkermansia muciniphila | AKK combined with cis-platinum could increase the levels of IFN-γ, IL-6 and TNF-α in peripheral blood and the spleen in mice, inhibit the expression of CD4+ CD25+ Foxp3+ Treg cells, and promote an antitumor immune response | [186] |
| CRC (CT26) | αPD-1 mAb | Akkermansia muciniphila | The glycerophospholipid generation produced by AKK bacteria affects the expression of IFN-γ and IL-2 in tumor microenvironment, resulting in different therapeutic effects of αPD-1 mAb | [148] |
| Melanoma (B16-F10); CRC (CT26) | Systemic IL-2 therapy | Akkermansia muciniphila | Amuc (AKK outer membrane protein) activates antitumor immunity through the TLR2 signaling pathway | [131] |
| CRC (AOM/DSS, MC38/CT26); Lewis lung cancer (LLC); melanoma (B16-F10) | With or without αPD-1 mAb | Clostridiales (Ruminococcaceae, Lachnospiraceae): Roseburia intestinalis; Eubacterium hallii; Faecalibacterium prausnitzii; Anaerostipes caccae | Clostridiales promote antitumor immune response in a CD8+ T dependent manner | [191] |
| CRC (MC38) | αPD-1 mAb | Lactobacillus paracasei sh2020 | Colonization of Lactobacillus paracasei sh2020 induces increased CXCL10 expression in tumors, which in turn promotes recruitment of CD8+ T cells and promotes an antitumor immune response | [192] |
| Melanoma (B16-F10); sarcoma (MCA205); CRC(MC38) | αPD-1 mAb; αCTLA-4 mAb | Enterococcus faecium; Enterococcus faecalis | Enterococcus with unique NlpC/P60 peptidoglycan hydrolase activity can produce peptides that activate NOD2 activity and modulate the efficacy of ICB therapy in vivo, promoting antitumor immunity | [193] |
| CRC (CT26) | αPD-1 mAb | Lactobacillus rhamnosus | Lactobacillus rhamnosus could effectively restore the gut microbiota depleted by antibiotics, significantly increase the relative abundance of beneficial bacteria, and promote the therapeutic effect of αPD-1 mAb | [194] |
| CRC (CT26) | Neoantigen cancer vaccine | Bifidobacterium (B. bifidum, B. longum, B. lactis and B. breve) | Bifidobacterium could affect the mechanism of tumor growth, change the composition of the gut microbiota, increase the abundance of antitumor Muribaculaceae, reduce the levels of tumor-promoting Lachnospiraceae, and promote the antitumor effect of a neoantigen cancer vaccine | [195] |
| CRC (MC38); sarcoma (MCA205); lung cancer (TC-1) | Cyclophosphamide; αPD-1 mAb | Enterococcus hirae | The tape measure protein (TMP) of the probacteriophage found in the genome of Enterococcus hirae phage contains an epitope that can bind MHC-I. After treatment with cyclophosphamide or αPD-1 mAb, mice carrying Enterococcus hirae developed TMP-specific H-2Kb restrictive CD8+ T-cell responses that ultimately promoted antitumor immunotherapy | [75] |
| Melanoma (B16); CRC (CT26) | αTIM-3 mAb | Enterococcus hirae; Lactobacillus johnsonii | Probiotic administration restored the antitumor activity of αTIM-3 mAb that was impaired by antibiotics usage | [183] |
| CRC (MC38); lymphoma (EG7) | αCD-47 mAb | Mixture of Bifidobacterium species (B. bifidum, B. longum, B. brevis, B. lactis) | Systemic administration of Bifidobacterium leads to its accumulation in tumors, which can effectively stimulate STING signal transduction, increase the cross-initiation of DCs after αCD-47 mAb treatment, and promote an antitumor immune response | [196] |
| Breast cancer (4T1); liver cancer (H22) | TGF-β blockade | Escherichia coli strain Nissle 1917 (EcN) | EcN colonization could effectively promote tumor-specific effector T-cell infiltration and DC activation after TGF-β blockade, resulting in a stronger antitumor effect | [197] |
| Melanoma (B16-F10) | αPD-1 mAb | Lactobacillus kefiranofaciens ZW18 (ZW18) | ZW18 activated the immunity, promoted tumor CD8+ T-cell infiltration, and significantly increased the abundance of Akkermansia, the Prevotellaceae_NK3B31_group and Muribaculum | [198] |
| CRC (MC38/CT26/HCT116); breast cancer (4T1) | αPD-1 mAb; oxaliplatin | Lactococcus lactis GEN3013 | L. lactis GEN3013 augmented cytotoxic immune cell populations, including CD4+ T cells, CD8+ effector T cells, and NK cells, in the tumor microenvironment | [199] |