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Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
Open accessAbstract
Gut microbes affect immunotherapy: The unleashing of antitumor T cell responses has ushered in a new era of cancer treatment. Although these therapies can cause dramatic tumor regressions in some patients, many patients inexplicably see no benefit. Mice have been used in two studies to investigate what might be happening. Specific members of the gut microbiota influence the efficacy of this type of immunotherapy (see the Perspective by Snyder et al. ). Vétizou et al. found that optimal responses to anticytotoxic T lymphocyte antigen blockade required specific Bacteroides spp. Similarly, Sivan et al. discovered that Bifidobacterium spp. enhanced the efficacy of antiprogrammed cell death ligand 1 therapy. Science , this issue, p. 1079 and p. 1084 ; see also p. 1031
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In the citing paper
“Mouse models have verified that Bifidobacteria, Bacteroides fragilis, and Burkholderia cepacia can ameliorate intestinal immunopathology in the context of anti-CTLA-4 therapy [17, 125, 126].”
From Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies (2022) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Second, exposures including medications, especially antibiotics and proton pump inhibitors, and diet that shape the microbiota are associated with ICI responses in patient cohorts and preclinical models.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Such as Bacteroides fragilis, Bacteroides thetaiotaomicron, Bifidobacterium, Akkermansia muciniphila and Faecalibacterium spp. have been shown to have favourable responses to cancer immunotherapy in both preclinical tumour models and patients with cancer.12–15”
From Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy (2022) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In mice receiving anti-CTLA-4 immunotherapy, antitumor immunity was dependent on the presence of specific Bacteroides species [7].”
From Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients (2019) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Both Bacteroides fragilis [31] and Bifidobacterium [32] were reported to promote the activation and maturation of DCs.”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [32]
In the citing paper
“Bacteroides fragilis enhanced the antitumor effect of CTLA-4 blockade by triggering DC maturation and stimulating IL-12-dependent Th1 cell immune responses [17].”
From Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies (2022) · cites this paper as [17]
In the citing paper
“Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs).”
From Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies (2022) · cites this paper as [17]
In the citing paper
“Supporting this contention, we and others reported that primary responses to anti-PD-1/ PD-L1 antibodies in patients with epithelial tumours and melanoma could, at least in part, be attributed to the taxonomic composition of the gut microbial ecosystem 18,20,25 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“Similarly, antibiotics (ATB) prior to ICI initiation drastically reduced the clinical benefit in several cohorts of patients across various cancer types (melanoma, advanced NSCLC, renal cell carcinoma (RCC), and urothelial cancer) 18,[20][21][22] .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“A diverse microbiota and the presence of specific bacteria such as Akkermansia muciniphila, Ruminococcus or Bifidobacterium genera were associated with improved clinical response to ICI, correlating with increased systemic immune tonus 18,20,25 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“These results support the possibility that Akk could promote the elicitation or recirculation of Th1 cells into the tumor microenvironment, as previously shown in mouse models 18,19 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“Akk was also overrepresented in patients with progression free-survival (PFS) > 3 months, when analyzing a subgroup of 60 patients with NSCLC 18 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“We previously reported the stool metagenomic profiling of 100 patients diagnosed with refractory NSCLC or RCC receiving second or third line anti-PD-1 antibodies, concluding that the prevalence of A. muciniphila (Akk) was increased in patients presenting partial response or stable disease, as compared with patients in progressive disease (61 versus 34% respectively, p=0.007) 18 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“We used MCA-205 fibrosarcomas because it is normally -in SPF eubiotic mice-sensitive to anti-PD-1 Ab and has been used as a reference mouse model in our previous avatar experiments reported in 18 and 37 , both papers showing that results obtained with MCA-205 were recapitulated in orthotopic TC1 lung cancer or RENCA RENal CArcinoma models, respectively.”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“These results expand on previous observations that have been made in smaller cohorts of patients with NSCLC 18,41 and provide evidence that gut microbiome diversity and composition, specifically the relative abundance of Akk, offer relevant information to predict survival of patients with NSCLC amenable to ICI.”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“Here, we provide preclinical data suggesting that Akk could therapeutically bypass the resistance to anti-PD-1 blockade conferred by FMT bereft of endogenous Akk (Extended Figure 6 and 17,18 ).”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“Of note, the 60 patients with NSCLC already described in our previous report 18 were excluded from the principal analysis.”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [18]
In the citing paper
“For immune checkpoint inhibition (ICI) therapy, mounting evidence suggests that the gut microbiome can determine patient treatment outcomes.”
From Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma (2020) · cites this paper as [13]
In the citing paper
“Recently, several studies have demonstrated that members of the gut microbiota are able to enhance the anti-tumor efficacy of PD-1 and CTLA4 blockade therapy6,7.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [6]
In the citing paper
“Recently, the gut microbiota has emerged as a potent new factor associated with the efficacy of anti–CTLA4, anti–PD-1, and anti–PD-L1 treatment (8-14).”
From Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy (2021) · cites this paper as [8]
In the citing paper
“These include TH1 immune responses directed at B. fragilis and A. muciniphila were associated with responses to the anti-CTLA4 antibody ipilimumab in patients with melanoma125 and to anti-PD-1 antibodies in patients with RCC or NSCLC, respectively42 (Table 1).”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [125]
In the citing paper
“These results confirm previous observations of biphasic effects for the Bacteroides genus dependent on the specific treatment agent(s) used9,40,41.”
From Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma (2024) · cites this paper as [41]
In the citing paper
“The intestinal microbiome has emerged as a tumor-extrinsic predictive biomarker to immune checkpoint blockade (ICB)1–6.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [2]
In the citing paper
“In mouse models, certain gut commensals mediate efficacy of anticancer therapies, including chemotherapy, radiotherapy, and immunotherapies such as adoptive T cell transfer, intratumoral CpG-oligonucleotides, and ICIs.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [5]
In the citing paper
“During CTLA-4 blockade in various cancers, Bacteroides fragilis triggers TLR2–4-dependent interleukin (IL)-12 release that is associated with anticancer effects.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [5]
In the citing paper
“as the gut and tumour microbiota can affect the survival of patients with cancer and their responses to therapy8,14,40–42,50”
From Identification of bacteria-derived HLA-bound peptides in melanoma (2021) · cites this paper as [50]
In the citing paper
“The role of the gut microbiome in modulating tumor responses to immunotherapy in melanoma [5–7], non-small cell lung cancer, renal cell carcinoma, and urothelial carcinoma [6, 8] has received increased attention across a series of studies in recent years.”
From Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma (2019) · cites this paper as [6]
In the citing paper
“On the contrary, tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade (180).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [180]
In the citing paper
“Moreover, in mice and patients, T cell responses specific for Bacteroides species, such as thetaiotaomicron or fragilis were associated with the efficacy of CTLA-4 blockade.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [180]
In the citing paper
“Bacteroides spp. have a protective effect on gastrointestinal toxicity during CTLA-4 mAb treatment.13”
In the citing paper
“The genus Bacteroides enhance the antitumour effect and alleviate the gastrointestinal toxicity in melanoma patients treated with CTLA-4 blockade.13”
In the citing paper
“Anti-CTLA-4 treatment was found to be ineffective in mice reared under sterile conditions and to induce a shift in the gut flora of conventionally reared mice.”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [97]
In the citing paper
“Further experiments showed that the presence of certain bacterial strains, in particular Bacteroides fragilis, promoted Th1 polarization in the animals and was associated with an improved anti-tumor immune response (97).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [97]
In the citing paper
“Anti-CTLA-4 treatment was found to be ineffective in mice reared under sterile conditions and to induce a shift in the gut flora of conventionally reared mice.”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [97]
In the citing paper
“In a similar study, administration of B. fragilis to sterile mice treated with anti-CTLA-4 resulted in reduced tumor growth, most likely by inducing a favorable shift toward Th1 responses (97).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [97]
In the citing paper
“Analysis of fecal samples revealed that the enrichment of specific gut commensals, such as Bifidobacterium [32] and Ruminococcaceae [33], had a significant positive correlation with CD8+T cell infiltration in the tumor bed or tumor-draining lymph node.”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [32]
In the citing paper
“Further analysis identified Bifidobacterium as a positive regulator of therapeutic response [32].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [32]
In the citing paper
“mice with different commensal microbes exhibited difference in melanoma growth rate and response to PD-L1 blockade, which could be eliminated by cohousing and fecal FMT [32].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [32]
In the citing paper
“B. fragilis and some Akkermansia species drive IL-12-dependent T H 1 responses in the context of CTLA4 or PD-1 blockade 22,48”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [48]
In the citing paper
“adjuvant signals mediated by microbial-associated molecular patterns acting on pattern recognition receptors expressed on host immune cells 30,48,49”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [48]
In the citing paper
“Adjuvant signals produced by the microbiota include lipopolysaccharide (LPS) and specific surface proteins (such as Amuc_1100 present on the surface of A. muciniphila62 ) that act on Toll-like receptors such as TLR4 and TLR2, respectively, thus increasing the immune tonus.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [48]
In the citing paper
“In oncology, converging findings demonstrate the negative impact of ATBinduced dysbiosis in mice.”
In the citing paper
“It is noteworthy that ATB-based conditionning of tumor bearing mice blunts the efficacy of PD-1 or PD-1 þ CTLA-4 blockade in otherwise 'normal' animals, suggesting a causal link between ATB and primary resistance to ICI and immunogenic chemotherapy [9,10,30,31].”
In the citing paper
“The microbiome has been described to majorly impact tumor immunity and response to ICI10–17”
From Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment (2023) · cites this paper as [11]
In the citing paper
“Other groups have also demonstrated differential bacterial signatures in the gut microbiome of patients who develop ICI-associated colitis14–16”
From Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis (2018) · cites this paper as [15]
In the citing paper
“Upon CTLA-4 blockade, intraepithelial lymphocytes damage ileal epithelial cells, stimulating the accumulation of Bacteroides fragilis and Burkholderiales spp., activating IL-12-producing dendritic cells ( D C s )a n dTh e l p e r1( T H 1) immune responses (13).”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“16S ribosomal RNA (rRNA)-based sequencing of gene amplicons and shotgun DNA sequencing of patient stool samples have identified subsets of bacteria more abundant in responding versus nonresponding patients.”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“Soon after, it was observed that several anticancer treatment modalities showed reduced therapeutic effects in germ-free mice as well as in mice treated with broad-spectrum antibiotics (11)(12)(13)(14), or in mice lacking specific immunepotentiating bacterial species originating from different vendors (15).”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“Given these considerations, it is perhaps even more striking that bacteria generally associated with health (such as Clostridiales, Ruminococcacae, Faecalibacterium spp., Akkermansia muciniphila, B. fragilis,a n dBifidobacteria) (13, 14, 18-20) or immunogenicity (Enterococci, Collinsella, and Alistipes)( 11, 13, 14, 20) were found to be abundant in responding patients.”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“However, the microbial stimulation of anticancer memory T H 1/Tc1 cell responses only partially rely on TLR2/TLR4 in the context of treatments with cyclophosphamide (16)o rC T L A -4b l o c k a d e ( 13).”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“In terms of effects on pattern recognition receptors, DCs exposed to microbes (such as B. fragilis or A. muciniphila) associated with anticancer properties induce systemic IL-12-dependent T H 1/Tc1 immune responses beneficial against tumors treated with antibody to CTLA-4 (13)orPD-1/PD-L1(14).”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“This effect depended on distinct Bacteroides species in melanoma treated with ipilimumab (13) and at least partly on Faecalibacterium (19)inmelanomaandonVerrucomicrobiacae [more specifically, A. muciniphila (14)] in lung cancer patients treated with the PD-1 inhibitors pembrolizumab or nivolumab.”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“Accordingly, B. fragilis and Burkholderia cepacia administered via gavage to mice reduced the severity of colitis induced by mAb to CTLA-4 (13,22).”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“Notably, fecal microbial transplantation (FMT) o ff e c e sf r o mp a t i e n t s( w h os h o w e dc l i n i c a lr esponse to immune checkpoint blockade) transferred a”
From The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies (2018) · cites this paper as [13]
In the citing paper
“Of note, antibiotics (except vancomycin),4”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as [12]
In the citing paper
“multiple studies demonstrated the negative impact of antibiotics in the context of treatment with ICB, likely due to their detrimental impact on gut microbial diversity”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Vetizou et al., 2015
In the citing paper
“Other bacteria like Enterococcus hirae (Viaud et al., 2013), Bacteroides fragilis (Vétizou et al., 2015), and Eubacterium sp. AM28-29 (Thomas et al., 2023) have been linked to improved responses in preclinical and clinical settings, often through mechanisms such as dendritic cell maturation and cytokine production (including IL-12).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Vétizou et al., 2015
In the citing paper
“More recently, its role in boosting ICB response was first demonstrated in mice when the gut microbiome’s influence on ICB success was suddenly recognized (Routy et al., 2018b, 2023; Vétizou et al., 2015).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Vétizou et al., 2015
In the citing paper
“For example, mouse studies have shown that B. fragilis can restore anti-CTLA-4 efficacy after antibiotic treatment or in germ-free mice (Vétizou et al., 2015).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Vétizou et al., 2015
In the citing paper
“Immune responses to other anticancer treatments, including CTLA-4 blockade194 and cyclophosphamide,195 were also associated with distinct gut microbiome configurations.”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [194]
In the citing paper
“Important initial insights came from murine models (Sivan et al., 2015, Vetizou et al., 2015), and many of these findings have now been validated in several patient cohorts treated with immunotherapy, specifically immune checkpoint blockade.”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“oral feeding with Bacteroides fragilis in combination with either Bacteroides thetaiotaomicron or Burkholderia cepacia augmented the action of anti-CTLA-4 therapy by eliciting a Th1 response in the lymph nodes and facilitating the maturation of intra-tumoral dendritic cells”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“FMT from patients having dominant Bacteroides species in their gut resulted in improved tumor control compared to FMT from patients with distinct Bacteroides or Prevotella species”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“The efficacy of anti-CTLA-4 therapy was markedly reduced in GF mice and SPF mice with broad-spectrum antibiotics.”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“Pre- clinical models have demonstrated an improvement in toxicity scores in anti-CTLA-4-treated mice with oral gavage of Bacteroides fragilis and Burkholderia cepacia”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“demonstrating that the composition of the gut microbiota could influence the response to immune checkpoint inhibitors targeting the cytotoxic T lymphocyte antigen-4 (CTLA-4) and the programmed death receptor-1 (PD-1)”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“notable changes in the abundance of gut microbiota in mice were seen following anti- CTLA-4 therapy, with a relative increase in Bacteroidales and Burkholderiales, and a decrease in Clostridiales”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Vetizou et al., 2015
In the citing paper
“In addition, fecal transplants from patients who benefitted clinically from anti-CTLA-4 therapy favored the growth of B. fragilis, linking this species with improved response.”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [99]
In the citing paper
“For example, in preclinical models, the therapeutic response to anti-CTLA-4 therapy was found to be dependent on Bacteroides species, as germfree mice or antibiotic-treated mice did not respond to anti-CTLA-4, but response was rescued through gavage of Bacteroides fragilis (99).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [99]
In the citing paper
“For example, mice transplanted with liquefied and filtered stool from patients with bacteroides‐rich microbiota population respond better to CTLA4 inhibitor treatment [431].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [431]
In the citing paper
“In GF or ATB-treated mice, activation of effector CD4+ T cells and TILs elicited by CTLA-4 blockade was considerably dampened.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“A combination of ATBs (ampicillin, colistin, and streptomycin) or imipenem alone destroyed the function of CTLA-4 inhibitors against the tumor.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“Moreover, recolonization of ATB-treated or GF mice with commensal bacteria, such as Bacteroides and Burkholderia genres, could restore the CTLA-4 blockade-mediated anticancer responses.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“In other words, management of gut microbiome elicits modification of TME and turns on a switch for the development of resistance to immune therapy, which enables tumor cells to escape immune surveillance.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“Interestingly, it was discovered that CTLA-4 blocking therapy could reverse the gut bacteria repertoire, causing a decrease in beneficial bacteria and an increase in bacteria that blunt the response to ipilimumab.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“In fact, dietary supplements with Bacteroides fragilis induced Th1 immune responses in the tumor-draining lymph nodes prompted the maturation of DCs in the TME and facilitated the restoration of the clinical response to CTLA-4 blockade.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“In this study, CTLA-4 blocking therapy was found to be effective against sarcoma, melanoma, and colon cancer in SPF mice but not in GF mice.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“These preliminary results showed that gut microbiota might be indispensable for the antitumor efficacy of anti-CTLA-4 treatment.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“Therefore, the production of cytokines may be one of the mechanisms used by the gut microbiome to alter resistance to therapy.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“The gut bacteria that significantly prolong PFS show a preserved cytokine response to PD-1-target treatment, whereas antibiotics have been demonstrated to decrease the level of cytokines in TME (67).”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“orally feeding B. fragilis induced Th1 immune response in the tumor-draining lymph nodes and catalyzed the maturation of DCs in the TME, facilitating the restoration of the clinical response to CTLA-4 blockade (67).”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [67]
In the citing paper
“Vetizou et al. demonstrated that the efficacy of anti-CTLA4 antibodies in reducing sarcoma tumor growth in mice is significantly increased when the gut microbiome is enriched in Bacteroides fragilis and Burkholderia cepacia [175].”
From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [175]
In the citing paper
“In animals, oral gavage of Bacterioides fragilis and Burkholderia cepacia demonstrated an amelioration of such immunotherapy-associated toxic side effects [175].”
From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [175]
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Immune Checkpoint Inhibitor–Mediated Diarrhea and Colitis: A Clinical Review
Gong, Z., & Wang, Y. (2020) · JCO Oncology Practice · doi:10.1200/op.20.00002 · Cited by 71
Potential Impacts of Prebiotics and Probiotics on Cancer Prevention
Samanta, S. (2020) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520621999201210220442 · Cited by 75
Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response
Zhang, H., Fu, L., Leiliang, X., Qu, C., Wu, W., Wen, R., Huang, N., He, Q., Cheng, Q., Liu, G., et al. (2024) · 癌症：英文版 · doi:10.1002/cac2.12597 · Cited by 74
Lin, A., Jiang, A., Huang, L., Yu, H., Zhang, C., Zhu, L., Mou, W., Liu, Z., Zhang, J., Cheng, Q., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2452277 · Cited by 74
“52,53 57 These alterations in bacterial strains may contribute to improved ICI efficacy.”
Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation
Sun, J., Song, S., Liu, J., Chen, F., Li, X., & Wu, G. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00678-x · Cited by 78
“Inaddition, Bacteroides havealso shownthepotentialtoenhancethetherapeuticeffectofCTLA-4blockersin melanoma patients, and the mechanism may involve speci fi c T-cell responses to B. thetaiotaomicron or B. fragilis 43 .”
Pharmacogenomics of off‐target adverse drug reactions
Garon, S. L., Pavlos, R. K., White, K. D., Brown, N. J., Stone, C. A., & Phillips, E. J. (2017) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13294 · Cited by 70
Connecting the Metabolic and Immune Responses to Cancer
Flint, T. R., Fearon, D. T., & Janowitz, T. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.001 · Cited by 71
Gut microbes contribute to variation in solid organ transplant outcomes in mice
Mcintosh, C. M., Chen, L., Shaiber, A., Eren, A. M., & Alegre, M. (2018) · Microbiome · doi:10.1186/s40168-018-0474-8 · Cited by 72
Meng, Y., Shi, X., Cai, L., Zhang, S., Ding, K., Nie, S., Luo, C., Xu, X., & Zhang, L. (2018) · Macromolecules · doi:10.1021/acs.macromol.8b02017 · Cited by 70
Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases
Cai, X., Zhan, H., Ye, Y., Yang, J., Zhang, M., Li, J., & Zhuang, Y. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.785153 · Cited by 66
“T cells can undergo spontaneous differentiation into Tfh cells in CTLA-4-deficient mice, while not in CD28-deficient mice, they might be applied to explain lethal multiorgan autoimmune symptoms in CTLA4−/− mice (Walker, 2017).”
BackgroundTallerico, R., Cristiani, C. M., Staaf, E., Garofalo, C., Sottile, R., Capone, M., de Coaña, Y. P., Madonna, G., Palella, E., Wolodarski, M., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1261242 · Cited by 68
“In previous studies in mice and in patients, antibiotics treatment weakened the antitumor response after anti-CTLA-4 blockade.(38) This was correlated with how certain bacteria in the normal gut flora influenced production of cytokines in co-cultures of T-cells and dendritic cells, e.”
BackgroundPorta, C., Sica, A., & Riboldi, E. (2017) · FEBS Journal · doi:10.1111/febs.14288 · Cited by 70
A Blueprint to Advance Colorectal Cancer Immunotherapies
Le, D. T., Hubbard-Lucey, V. M., Morse, M. A., Heery, C. R., Dwyer, A. J., Marsilje, T. H., Brodsky, A. N., Chan, E. W., Deming, D. A., Diaz, L. A., et al. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0375 · Cited by 71
Hylander, B. L., & Repasky, E. A. (2019) · International Journal of Hyperthermia · doi:10.1080/02656736.2019.1647356 · Cited by 69
Chyuan, I., Chu, C., & Hsu, P. (2021) · Cancers · doi:10.3390/cancers13061188 · Cited by 68
“Similarly, a study noted that the antitumor effects of CTLA-4 blockade were dependent on specific Bacteroides species [80].”
BackgroundOverview of microbial profiles in human hepatocellular carcinoma and adjacent nontumor tissues
He, Y., Zhang, Q., Yu, X., Zhang, S., & Guo, W. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-03938-6 · Cited by 70
Joachim, L., Göttert, S., Sax, A., Steiger, K., Neuhaus, K., Heinrich, P., Fan, K., Orberg, E. T., Kleigrewe, K., Ruland, J., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104834 · Cited by 72
“19 We were able to reproduce these observations with increased cleavage of caspase-3 in large intestinal tissue sections from mice undergoing anti-CTLA-4 treatment as a sign of therapy-induced apoptosis of intestinal cells (Fig.”
BackgroundInfluentialMevalonate Metabolism in Immuno-Oncology
Gruenbacher, G., & Thurnher, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01714 · Cited by 76
“Intriguingly, the efficacy of anti-CTLA-4 in mouse melanoma models depended on the microbiota of these mice (58), raising the important question of how the microbiota affects immunometabolism.”
BackgroundBeyond PD-L1 Markers for Lung Cancer Immunotherapy
Wojas‐Krawczyk, K., Kalinka‐Warzocha, E., Grenda, A., Krawczyk, P. A., & Milanowski, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081915 · Cited by 71
“found that tumors in antibiotics-treated or germ-free mice did not respond to CTLA-4 blockade [73].”
BackgroundSensitizing the Tumor Microenvironment to Immune Checkpoint Therapy
Zemek, R. M., Chin, W. L., Nowak, A. K., Millward, M., Lake, R., & Lesterhuis, W. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00223 · Cited by 73
“fragilis have shown to improve antitumor cytotoxic T-cell immunity improving the efficacy of anti-CTLA-4 in multiple cancer mouse models (121).”
BackgroundXia, W., Khan, I., Li, X., Huang, G., Yu, Z., Leong, W. K., Han, R., Ho, L. T., & Hsiao, W. L. W. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104809 · Cited by 70
Role of Oral Bacteria in the Development of Oral Squamous Cell Carcinoma
Li, Q., Hu, Y., Zhou, X., Liu, S., Han, Q., & Cheng, L. (2020) · Cancers · doi:10.3390/cancers12102797 · Cited by 71
Rezasoltani, S., Yadegar, A., Aghdaei, H. A., & Zali, M. R. (2020) · Cancer Medicine · doi:10.1002/cam4.3694 · Cited by 67
Smectite promotes probiotic biofilm formation in the gut for cancer immunotherapy
Han, C., Song, J., Hu, J., Fu, H., Feng, Y., Mu, R., Xing, Z., Wang, Z., Wang, L., Zhang, J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108706 · Cited by 69
Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy
Wu, J., Wang, S., Zheng, B. J., Qiu, X., Wang, H., & Chen, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.669150 · Cited by 72
“The relevant bacteria such as Bifidobacterium (18), Bacteroides fragilis (19), Akkermansia muciniphia (20) are found to be related to the clinical outcomes of cancer immunotherapy.”
BackgroundInfluentialYang, F., Wang, J., Wang, Y., Liu, B., & Molina, J. R. (2021) · Cancers · doi:10.3390/cancers14010109 · Cited by 73
The potential role of the microbiota in prostate cancer pathogenesis and treatment
Pernigoni, N., Guo, C. W., Gallagher, L., Yuan, W., Colucci, M., Troiani, M., Liu, L., Maraccani, L., Guccini, I., Migliorini, D., et al. (2023) · Nature Reviews Urology · doi:10.1038/s41585-023-00795-2 · Cited by 72
“…modulating the gut microbiota can enhance T cell-mediated antitumour activity of anti-PD1 and anti-CTLA4 antibodies in melanoma and sarcoma mouse models 9,48,51 ; this has led to several clinical trials combining therapies modulating the gut microbiota with these more established treatments 179 .”
BackgroundInfluentialNavigating established and emerging biomarkers for immune checkpoint inhibitor therapy
Wang, S. L., & Chan, T. A.-T. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.03.006 · Cited by 80
Wang, S., Li, H., Li, B., Xie, T., Zhu, T., Sun, L., Ren, H., & Ye, Z. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.05.016 · Cited by 67
Rogers, M. B., Aveson, V. G., Firek, B., Yeh, A., Brooks, B., Brower–Sinning, R., Steve, J., Banfield, J. F., Zureikat, A. H., Hogg, M. E., et al. (2016) · Pancreas · doi:10.1097/mpa.0000000000000726 · Cited by 70
Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma
Hargadon, K. M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01594 · Cited by 69
“In other work investigating microbial influences on checkpoint blockade therapy, pretreatment of mice with a cocktail of broad-spectrum antibiotics blocked the efficacy of α-CTLA-4 Ab therapy for established Ret murine melanomas (196).”
BackgroundCholecystectomy Damages Aging-Associated Intestinal Microbiota Construction
Wang, W., Wang, J., Li, J., Yan, P., Jin, Y., Zhang, R., Yue, W., Guo, Q., & Geng, J. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01402 · Cited by 70
“Inhabitants in the human intestine can strongly affect development, health, and disease, such as cancer, as well as responses to anticancer immunotherapy (Sommer and Bäckhed, 2013; Viaud et al., 2013; Sivan et al., 2015; Vétizou et al., 2015; Brennan and Garrett, 2016).”
BackgroundChen, J., Levy, A., Tian, A.-L., Huang, X., Cai, G., Fidelle, M., Rauber, C., Ly, P., Pizzato, E., Sitterle, L., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.02.010 · Cited by 67
Self-citationProbiotic species in the modulation of the anticancer immune response
Marinelli, L., Tenore, G. C., & Novellino, E. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.08.007 · Cited by 64
Saftien, A., Puschhof, J., & Elinav, E. (2023) · Gut · doi:10.1136/gutjnl-2022-327952 · Cited by 67
Bacteria-based immunotherapy for cancer: a systematic review of preclinical studies
Zhou, M., Tang, Y., Xu, W., Hao, X., Li, Y., Huang, S. Q., Xiang, D., & Wu, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1140463 · Cited by 73
“Besides, adoptive metastasis specific to Bacteroides fragilis T cells can address the ineffectiveness of CTLA-4 blockade, which occurs in antibiotic-treated conditions or a sterile tumor setting (105).”
The role of the gut microbiota in tumor, immunity, and immunotherapy
Xie, Y., & Liu, F. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1410928 · Cited by 75
“Moreover, oral administration of Mycobacterium fragilis along with Bacteroides thetaiotaomicron or Burkholderia cepacia enhanced the effects of anti-CTLA-4 therapy by stimulating Th1 responses in lymph nodes and promoting intratumoral dendritic cell maturation (136) (Figure 3).”
BackgroundInfluentialCao, M., Deng, Y., Hao, Q., Yan, H., Wang, Q., Dong, C., Wu, J., He, Y., Huang, L., Xia, X., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02226-7 · Cited by 76
“11,15,17,19,29 As validation, CT26 cells also exhibited sensitivity to PD-1 inhibitor treatment when initiated with a smaller tumor volume, 30 while the ef fi cacy was signi fi cantly diminished upon depletion of the gut microbiota (Supplementary Fig.”
Fernandez, E., Wargo, J. A., & Helmink, B. A. (2025) · JAMA · doi:10.1001/jama.2025.2191 · Cited by 82
Liu, X., Wang, L., Jing, N., Jiang, G., & Liu, Z. (2020) · Microorganisms · doi:10.3390/microorganisms8020175 · Cited by 68
Drug Discovery via Human-Derived Stem Cell Organoids
Liu, F., Huang, J., Ning, B., Liu, Z., Chen, S., & Zhao, W. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00334 · Cited by 69
“In vitro models Research area Finding References Co-culture with lymphocytes Cancer immunotherapy Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocker relies on the microbiota in anticancer immunotherapy Vetizou et al., 2015”
BackgroundInfluentialImmune‑related adverse events during anticancer immunotherapy: Pathogenesis and management (Review)
Stucci, L. S., Palmirotta, R., Passarelli, A. M., Silvestris, E., Argentiero, A., Lanotte, L., Acquafredda, S., Todisco, A., & Silvestris, F. (2017) · Oncology Letters · doi:10.3892/ol.2017.6919 · Cited by 67
“A previous study has described the association between variations in gut microbiota and the efficacy of immunotherapy with anti-CTLA4 and anti-PD1/PD-L1 checkpoint inhibitors, whose responsiveness is variable among patients (68).”
Traditional Chinese Medicine and Gut Microbiome: Their Respective and Concert Effects on Healthcare
Zhang, R., Gao, X., Bai, H., & Ning, K. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00538 · Cited by 68
“In mice, the procarcinogenic phenotype expressed by genetically mutated mice has been shown to be transferred to wild-type mice by microbiome transfer (Garrett et al., 2009; Couturier-Maillard et al., 2013; Hu et al., 2013) , and transfer of fecal microbiome from patients who are sensitive to cancer treatment into ger…”
BackgroundZhu, R., Lang, T., Yan, W., Zhu, X. G., Huang, X. Y., Yin, Q., & Li, Y. (2021) · Advanced Science · doi:10.1002/advs.202003542 · Cited by 65
The interplay of obesity, gut microbiome and diet in the immune check point inhibitors therapy era
Spyrou, N., Vallianou, N. G., Kadillari, J., & Dalamaga, Μ. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.008 · Cited by 66
Amodio, V., Mauri, G., Reilly, N. M., Bianchi, A. S., Siena, S., Bardelli, A., & Germano, G. (2021) · Cancers · doi:10.3390/cancers13112638 · Cited by 67
“Concomitantly, in both a pre-clinical sarcoma model and in metastatic melanoma patients, the group of Zitvogel and coworkers revealed that the efficacy of anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) and T cell infiltration was dependent on the presence of Bacteroides Thetaiotaomicron or Bacteroides fragilis [5…”
BackgroundRenal Cell Cancer – Insights in Drug Resistance Mechanisms
AWEYS, H., LEWIS, D., Sheriff, M., Rabbani, R. D., Lapitan, P., Sanchez, E., Papadopoulos, V. P., Ghose, A., & Boussios, S. (2023) · Anticancer Research · doi:10.21873/anticanres.16675 · Cited by 71
“ICI-mediated antiangiogenic therapy in the treatment of metastatic RCC involves suppressing the production of proangiogenic factors or inhibiting their binding to their respective receptors, thereby halting angiogenesis (31).”
BackgroundBifidobacterium modulation of tumor immunotherapy and its mechanism
Pei, B., Peng, S., Huang, C., & Zhou, F. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03665-x · Cited by 71
“Another study examined the effect of vancomycin in combination with DSS and anti-CTLA4 and showed that mice in the combination treatment group had significantly lower histopathology scores than those in the control group [72].”
BackgroundPrasad, R., Rehman, A., Rehman, L., Darbaniyan, F., Blumenberg, V., Schubert, M., Mor, U., Zamir, E., Schmidt, S., Hayase, T., et al. (2024) · Blood · doi:10.1182/blood.2024025366 · Cited by 69
Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial
Davar, D., Morrison, R. M., Dzutsev, A., Karunamurthy, A. D., Chauvin, J.-M., Amatore, F., Deutsch, J. S., das Neves, R. X., Rodrigues, R. R., McCulloch, J. A., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.10.007 · Cited by 75
Zhong, H., Jiang, J., Hussain, M., Zhang, H., Ling, C., & Guan, R. (2025) · Advanced Science · doi:10.1002/advs.202500304 · Cited by 75
Inflammation, Microbiota, and Prostate Cancer
Puhr, M., Marzo, A. M. D., Isaacs, W. B., Lucia, M. S., Sfanos, K. S., Yegnasubramanian, S., & Čulig, Z. (2016) · European Urology Focus · doi:10.1016/j.euf.2016.08.010 · Cited by 66
“[15] Vetizou M, Pitt JM, Dalliere R, et al.”
BackgroundIntestinal microbiota: a novel perspective in colorectal cancer biotherapeutics
Ding, C., Tang, W., Fan, X., & Wu, G. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s170626 · Cited by 68
“Moreover, IM has been found to play a significant modulation role in immune-checkpoint inhibitors-mediated anticancer immune response.(36,37) In clinical trials, pro-/prebiotics are widely used to reduce postoperative infections, and improve bowel immune system and epithelial barrier function in CRC patients.”
Rossi, G., Pezzuto, A., Sini, C., Tuzi, A., Citarella, F., McCusker, M. G., Nigro, O., Tanda, E. T., & Russo, A. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.07.005 · Cited by 66
Airway Microbiota as a Modulator of Lung Cancer
Goto, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093044 · Cited by 67
Randrian, V., Evrard, C., & Tougeron, D. (2021) · Cancers · doi:10.3390/cancers13123063 · Cited by 65
Manipulation of Innate and Adaptive Immunity through Cancer Vaccines
Sayour, E. J., & Mitchell, D. A. (2017) · Journal of Immunology Research · doi:10.1155/2017/3145742 · Cited by 64
Dzobo, K., & Dandara, C. (2020) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2020.0023 · Cited by 65
“Recently, studies also demonstrated the gut microbiota’s influence on cancer response to therapy through modulation of TME (Iida et al., 2013; Ve´tizou et al., 2015).”
Immunotherapy in Pancreatic Adenocarcinoma: Beyond “Copy/Paste”
Hester, R., Mazur, P. K., & McAllister, F. M. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0900 · Cited by 67
“been extensively studied in several tumor types (80-83).”
BackgroundShaping functional gut microbiota using dietary bioactives to reduce colon cancer risk
Seidel, D., Azcárate-Peril, M. A., Chapkin, R. S., & Turner, N. D. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.06.009 · Cited by 64
The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts
Hov, J., & Karlsen, T. (2017) · Seminars in Liver Disease · doi:10.1055/s-0037-1608801 · Cited by 65
Sen, S., Pestana, R. C., Hess, K. R., Viola, G. M., & Subbiah, V. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy453 · Cited by 65
“Previous reports suggest a potential relevance of microbiologic factors in the clinical activity of these drugs [1, 3, 5].”
BackgroundGut Microbiome Modulates Response to Cancer Immunotherapy
Khan, M. A. W., Ologun, G. O., Arora, R., McQuade, J. L., & Wargo, J. A. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06111-x · Cited by 69
Considerations for successful cancer immunotherapy in aged hosts
Hurez, V, Padrón, Á. S., Svatek, R. S., & Curiel, T. J. (2016) · Clinical and Experimental Immunology · doi:10.1111/cei.12875 · Cited by 65
Pancreatic Cancer, Gut Microbiota, and Therapeutic Efficacy
Zhang, X., Liu, Q., Liao, Q., & Zhao, Y. (2020) · Journal of Cancer · doi:10.7150/jca.37445 · Cited by 68
“[49] CTLA-4 Bacteroides thetaiotaomicron, Bacteroides fragilis Beneficial Elicit Th1 immune response and DC maturation”
BackgroundInamura, K. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.06.006 · Cited by 63
Stimulators of immunogenic cell death for cancer therapy: focusing on natural compounds
Amiri, M., Molavi, O., Sabetkam, S., Jafari, S., & Montazersaheb, S. (2023) · Cancer Cell International · doi:10.1186/s12935-023-03058-7 · Cited by 67
“Based on this review, gut bacteria have a modulatory impact on immunity and are critical for the effectiveness of anticancer drugs [126–128].”
BackgroundA guide to germ‐free and gnotobiotic mouse technology to study health and disease
Jans, M., & Vereecke, L. (2024) · FEBS Journal · doi:10.1111/febs.17124 · Cited by 67
“…of specific commensal bacteria in immunotherapy efficacy was highlighted by Vetizou and colleagues, as GF mice failed to respond to CTLA-4 blockade therapy until supplemented with Bacteroides fragilis , underscoring Bacteroidales’ significance in the immunostimulatory effects of anti-CTLA-4 ICI [202].”
Pitt, J. M., Vétizou, M., Boneca, I. G., Lepage, P., Chamaillard, M., & Zitvogel, L. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1132137 · Cited by 65
“This protection was associated with the capacity of B. fragilis to promote the proliferation of ICOS+ Treg in the lamina propria, possibly via mobilizing plasmacytoid DC seen to accumulate and mature in mesenteric lymph nodes after B. fragilis monocolonization of GF mice treated with anti-CTLA4 Ab.5,8 In support of th…”
Self-citationNot Just Antibiotics: Is Cancer Chemotherapy Driving Antimicrobial Resistance?
Papanicolas, L. E., Gordon, D., Wesselingh, S. L., & Rogers, G. B. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.10.009 · Cited by 68
McQuade, J. L., Ologun, G. O., Arora, R., & Wargo, J. A. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-00913-y · Cited by 63
Zeb2 drives invasive and microbiota-dependent colon carcinoma
Slowicka, K., Πέττα, Ι., Blancke, G., Hoste, E., Dumas, E., Sze, M., Vikkula, H., Radaelli, E., Haigh, J. J., Jonckheere, S., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0070-2 · Cited by 64
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Caenepeel, C., Tabib, N. S. S., Vieira‐Silva, S., & Vermeire, S. (2020) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16096 · Cited by 65
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Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances
Kim, H. J., & Kim, Y. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052984 · Cited by 69
Mutanome directed cancer immunotherapy
Vormehr, M., Diken, M., Boegel, S., Kreiter, S., Türeci, Ÿ., & Şahin, U. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.12.001 · Cited by 66
“viral antigens) [52], the tumor microenvironment [53] and the gut microbiota [54] seem to have a role.”
Kaderbhaï, C., Tharin, Z., & Ghiringhelli, F. (2019) · Cancers · doi:10.3390/cancers11020201 · Cited by 63
“Seminal observations from Laurence Zitvogel group underline in mouse preclinical models that checkpoint inhibitors lose their antitumor efficacy in germ free mice or mice treated with large spectrum antibiotics [71].”
BackgroundHe, X., Du, Y., Wang, Z., Wang, X., Duan, J., Wan, R., Xu, J., Zhang, P., Wang, D., Tian, Y., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000807 · Cited by 64
Targeting the Gut Microbiome to Mitigate Immunotherapy-Induced Colitis in Cancer
Chang, A. E., Golob, J. L., Schmidt, T. M., Peltier, D. C., Lao, C. D., & Tewari, M. (2021) · Trends in Cancer · doi:10.1016/j.trecan.2021.02.005 · Cited by 62
Nenclares, P., Bhide, S., Sandoval‐Insausti, H., Pialat, P.-M., Gunn, L., Melcher, A. A., Newbold, K. L., Nutting, C. M., & Harrington, K. J. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.02.047 · Cited by 62
PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies
Mucileanu, A., Chira, R. I., & Mircea, P. A. (2021) · Medicine and Pharmacy Reports · doi:10.15386/mpr-2116 · Cited by 60
“Therefore, modulation of the microbiota is a potential strategy to enhance the efficacy of immunotherapy [88,89].”
BackgroundIntestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration
Zhou, Y., Medik, Y. B., Patel, B., Zamler, D. B., Chen, S., Chapman, T., Schneider, S. M., Park, E. M., Babcock, R. L., Chrisikos, T. T., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20221333 · Cited by 63
“…colitis The intestinal microbiome is linked with antitumor response to ICB, irAEs, and non-ICB-associated intestinal inflammation (Cheng et al., 2020; Dubin et al., 2016; Gopalakrishnan et al., 2018a; Gopalakrishnan et al., 2018b; McCulloch et al., 2022; V´etizou et al., 2015; Wang et al., 2018).”
Dadgar-Zankbar, L., Elahi, Z., Shariati, A., Khaledi, A., Razavi, S., & Khoshbayan, A. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01909-y · Cited by 68
Recent success and limitations of immune checkpoint inhibitors for cancer: A lesson from melanoma
Ottaviano, M., De Placido, S., & Ascierto, P. A. (2019) · Virchows Archiv · doi:10.1007/s00428-019-02538-4 · Cited by 57
The Microbiome and Prostate Cancer Risk
Wheeler, K. M., & Liss, M. A. (2019) · Current Urology Reports · doi:10.1007/s11934-019-0922-4 · Cited by 62
Prevotella copri is associated with carboplatin-induced gut toxicity
Yu, C., Zhou, B., Xia, X., Chen, S., Deng, Y., Wang, Y., Wu, L., Tian, Y., Zhao, B., Xu, H., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1963-9 · Cited by 62
Fujiwara, Y., Mittra, A., Naqash, A. R., & Takebe, N. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.11 · Cited by 67
“Fecal microbial transplantation from patients with good response to anti-CTLA-4 antibody and supplementation of Bacteroides species to germ-free mice resulted in improved response to anti-CTLA-4 antibody([193]).”
BackgroundPeiffer, L. B., White, J. R., Jones, C. B., Slottke, R., Ernst, S. E., Moran, A. E., Graff, J. N., & Sfanos, K. S. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100822 · Cited by 63
Role of the tumor microenvironment in cancer hallmarks and targeted therapy (Review)
Naser, R., Fakhoury, I., El‑Fouani, A., Abi‑Habib, R., & El‑Sibai, M. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5471 · Cited by 61
The Impact of Gut Microbiota-Derived Metabolites on the Tumor Immune Microenvironment
Luu, M., Schütz, B., Lauth, M., & Visekruna, A. (2023) · Cancers · doi:10.3390/cancers15051588 · Cited by 65
“found that enhanced anti-cancer immunotherapy relies on the presence of Bacteroides fragilis or Bacteroides thetaiotaomicron within the gut microbiome [30].”
BackgroundDóra, D., Ligeti, B., Kovács, T., Revisnyei, P., Gálffy, G., Dulka, E., Krizsán, D., Kalcsevszki, R., Megyesfalvi, Z., Döme, B., et al. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2204746 · Cited by 63
Morowitz, M. J., Caro, V. D., Pang, D., Cummings, J. L., Firek, B., Rogers, M. B., Ranganathan, S., Clark, R. S. B., & Aneja, R. K. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002291 · Cited by 61
Borcherding, N. C., Kolb, R. H., Gullicksrud, J. A., Vikas, P., Zhu, Y., & Zhang, W. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.030 · Cited by 60
“Use of antibiotics has been associated with a reduction in efficacy of ICB in mice and humans.[153, 154] Responders receiving PD-1 blockade have increased species in the Firmicutes, Verrucomicrobia, and Actinobacteria phyla.”
Oh, H. J., Kim, J. H., Bae, J. M., Kim, H. J., Cho, N., & Kang, G. H. (2018) · Journal of Pathology and Translational Medicine · doi:10.4132/jptm.2018.11.29 · Cited by 63
Longo, V., Brunetti, O., Azzariti, A., Galetta, D., Nardulli, P., Leonetti, F., & Silvestris, N. (2019) · Cancers · doi:10.3390/cancers11040539 · Cited by 61
“[15] found that antitumor effects of anti-CTLA-4 mAb depended on distinct samples of Bacteroides (B).”
BackgroundPowell, N., Ibraheim, H., Raine, T., Speight, A., Papa, S., Brain, O., Green, M., Samaan, M., Spain, L. A., Yousaf, N., et al. (2020) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(20)30014-5 · Cited by 63
Mangan, B. L., McAlister, R. K., Balko, J. M., Johnson, D. B., Moslehi, J. J., Gibson, A., & Phillips, E. J. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14433 · Cited by 62
“demonstrated that supplementation of certain gut microbiota such as Bacteroides fragilis and Burkholderia cepacia resulted in improvement of toxicity in preclinical models of mice treated with CTLA-4 inhibitors.(91)”
BackgroundCrosstalk between circadian rhythms and the microbiota
Pearson, J. A., Wong, F. S., & Li, W. (2020) · Immunology · doi:10.1111/imm.13278 · Cited by 60
Metadata
- Authors
- Vétizou, M., Pitt, J. M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M. P., Duong, C. P. M., Poirier-Colame, V., Roux, A., Becharef, S., Formenti, S., Golden, E., Cording, S., Eberl, G., Schlitzer, A., Ginhoux, F., Mani, S., Yamazaki, T., Jacquelot, N., Enot, D. P., Bérard, M., Nigou, J., Opolon, P., Eggermont, A., Woerther, P.-L., Chachaty, E., Chaput, N., Robert, C., Mateus, C., Kroemer, G., Raoult, D., Boneca, I. G., Carbonnel, F., Chamaillard, M., & Zitvogel, L.
- Affiliations
- Université Paris-Sud (FR)
- Microbiologie de l’alimentation au service de la santé (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France.
- New York University (US)
- Institut Pasteur (FR)
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France.
- Agency for Science, Technology and Research (SG)
- Albert Einstein College of Medicine (US)
- Institut Gustave Roussy (FR)
- Animalerie Centrale, Institut Pasteur, Paris, France.
- Service de microbiologie, GRCC, Villejuif, France.
- Université de la Méditerranée Aix-Marseille II (FR)
- Corresponding author
- Boneca, Ivo Gomperts
- Carbonnel, Franck
- Chamaillard, Mathias
- Zitvogel, Laurence
- ORCID
- Vétizou, Marie
- Daillère, Romain
- Lepage, Patricia
- Flament, Caroline
- Rusakiewicz, Sylvie
- Routy, Bertrand
- Duong, Connie P. M.
- Roux, Antoine
- Becharef, Sonia
- Formenti, Silvia
- Cording, Sascha
- Schlitzer, Andreas
- Ginhoux, Florent
- Mani, Sridhar
- Yamazaki, Takahiro
- Jacquelot, Nicolas
- Nigou, Jérôme
- Opolon, Paule
- Eggermont, Alexander
- Woerther, Paul-Louis
- Chaput, Nathalie
- Robert, Caroline
- Kroemer, Guido
- Raoult, Didier
- Boneca, Ivo Gomperts
- Carbonnel, Franck
- Chamaillard, Mathias
- Zitvogel, Laurence
- Venue
- Science
- Published
- 2015-11-27
- Volume
- 350
- Issue
- 6264
- Pages
- 1079-1084
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4721659
- OpenAlex
- W2165456770
- Cited by
- 3,488
- References
- 35
- Citations by year
- 2026: 239 · 2025: 332 · 2024: 340 · 2023: 406 · 2022: 416 · 2021: 398 · 2020: 386 · 2019: 303 · 2018: 280 · 2017: 223 · 2016: 147 · 2015: 13
- FWCI
- 96.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- Funders
- European Commission
- Agence Nationale de la Recherche (ANR-10-LABX-0015, ANR-10-IBHU-0001)
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Fondation de France
- Institut National Du Cancer
- Institut Gustave-Roussy
- Swiss Bridge Foundation
- National Cancer Institute (R01CA161879)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CTLA-4 blockade, cancer immunotherapy, gut microbiota, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroidales, melanoma, germ-free mice, fecal microbiota transplantation, adoptive T cell therapy, T cell response, antibiotic therapy
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Ipilimumab, Adult, Aged, Aged, 80 and over, Animals, Anti-Bacterial Agents, Antibodies, Monoclonal, Bacteroides, Female, Germ-Free Life, Humans, Immunologic Memory, Immunotherapy, Intestines, Male, Melanoma, Mice, Inbred C57BL, Middle Aged, Skin Neoplasms, T-Lymphocytes, Mice, CTLA-4 Antigen, Dysbiosis
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