Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

Derosa, Lisa; Routy, Bertrand; Fidelle, Marine; Iebba, Valerio; Alla, Laurie; Pasolli, Edoardo; Segata, Nicola; Desnoyer, Aude; Pietrantonio, Filippo; Ferrere, Gladys; Fahrner, Jean-Eudes; Chatellier, Emmanuelle Le; Pons, Nicolas; Galleron, Nathalie; Roume, Hugo; Duong, Connie P.M.; Mondragón, Laura; Iribarren, Kristina; Bonvalet, Mélodie; Terrisse, Safae; Rauber, Conrad; Goubet, Anne-Gaëlle; Daillère, Romain; Lemaître, Fabien; Reni, Anna; Casu, Beatrice; Alou, Maryam Tidjani; Silva, Carolina Alves Costa; Raoult, Didier; Fizazi, Karim; Escudier, Bernard; Kroemer, Guido; Albigès, Laurence; Zitvogel, Laurence

doi:10.1016/j.eururo.2020.04.044

Cited by 209 publications

(206 citation statements)

References 52 publications

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“…[28][29][30][31][32][33][34][35][36] Recently, corroborating this notion, Derosa et al confirmed in a prospective trial investigating the composition of the gut microbiota through shotgun metagenomics that antibiotics prior to second-line PD-1 blockade in advanced RCC patients had a deleterious clinical impact, reducing the microbiota diversity, and increasing Clostridium hathewayi, a species associated with immune tolerance. 37 In parallel, microbiota profiling from 70 Japanese NSCLC patients also showed that ATB prior to ICIs decreases bacterial diversity and increases Clostridium hathewayi. 38 Intrinsically, identification of key bacteria driving the sensitivity/primary resistance to anticancer treatments is crucial to unravel the role of the gut microbiota in this scenario.…”

Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 94%

“…Many of the recently published studies in this area highlight the deleterious effect of antibiotics in patients with more advanced disease and with multifariousness incidents that may influence ICI responses. 28,37 However, a recent analysis showed that patients with non-metastatic melanoma, a "best-prognosis" subgroup receiving ICIs in the adjuvant setting, also had a survival detriment if exposed to antibiotics. Clearly, harm from antibiotics is not limited to cancer patients with advanced metastatic disease.…”

Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 99%

“…Conversely, there is strong evidence indicating that antibiotics-induced dysbiosis is associated with poor therapeutic efficacy of ICI-based immunotherapy, suggesting a causal link between dysbiosis and poor therapeutic outcome. [28][29][30][31][32][33]36,37…”

Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 99%

“…51 Several teams have confirmed the potential clinical significance of Akkermansia muciniphila in driving a therapeutic benefit to ICIs, more specifically in NSCLC, 28 melanoma, 46 HCC patients, 52 and recently in RCC. 37,53 In brief, Derosa et al reported in 58 RCC cancer patients treated in 2 L with nivolumab that a significant bacterial composition contrasted R versus NR with an overrepresentation of distinct species including Akkermansia muciniphila, Bacteroides salyersiae, or Eubacterium siraeum in patients disposed to becoming R. 37 In a parallel study, all RCC cancer patients exhibiting a complete response to ICIs (n = 3) harbored Akkermansia muciniphila although the number of patients was not sufficient to draw definitive conclusions. 53 Fecal metagenomics analysis performed in 8 HCC cancer patients identified Akkermansia muciniphila and Ruminococcaceae spp.…”

Section: Gut Oncomicrobiota Signatures Associated With Response To Icismentioning

confidence: 99%

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Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

et al. 2020

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Accumulating evidence from preclinical studies and human trials demonstrated the crucial role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade. In summary, it appears that a diverse intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota composition that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. In this review, we explore preclinical and translational studies highlighting how eubiotic and dysbiotic microbiota composition can affect progression-free survival in cancer patients.

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Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 94%

Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 99%

Section: Antibiotics Hinder the Efficacy Of Icismentioning

confidence: 99%

Section: Gut Oncomicrobiota Signatures Associated With Response To Icismentioning

confidence: 99%

See 2 more Smart Citations

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

et al. 2020

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“…Regarding response to ICIs, through the analysis of fecal samples and gut bacteria identification, several authors showed that bacteria composition correlated with immunotherapy response in the treatment of melanoma ( 183 – 185 ), renal cell carcinoma ( 118 , 186 ) or NSCLC ( 118 ).…”

Section: Gut Microbiome As Biomarkers Of Irae and Ici-induced Akimentioning

confidence: 99%

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

et al. 2020

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Immune checkpoint inhibitors (ICIs) are a novel class of immunotherapy drugs that have improved the treatment of a broad spectrum of cancers as metastatic melanoma, non-small lung cancer or renal cell carcinoma. These humanized monoclonal antibodies target inhibitory receptors (e.g. CTLA-4, PD-1, LAG-3, TIM-3) and ligands (PD-L1) expressed on T lymphocytes, antigen presenting cells and tumor cells and elicit an anti-tumor response by stimulating immune system. Nevertheless, the improved overall survival is complicated by the manifestation of Immune-related Adverse Effects (irAEs). During treatment with ICIs, the most common adverse kidney effect is represented by the development of acute kidney injury (AKI) with the acute tubulointerstitial nephritis as recurrent histological feature. The mechanisms involved in ICIs-induced AKI include the re-activation of effector T cells previously stimulated by nephrotoxic drugs (i.e. by antibiotics), the loss of tolerance versus self-renal antigens, the increased PD-L1 expression by tubular cells or the establishment of a pro-inflammatory milieu with the release of self-reactive antibodies. For renal transplant recipient treated with ICIs, the increased incidence of rejection is a serious concern. Therefore, the combination of ICIs with mTOR inhibitors represents an emerging strategy. Finally, it is relevant to anticipate which patients under ICIs would experience severe irAEs and from a kidney perspective, to predict patients with higher risk of AKI. Here, we provide a detailed overview of ICIs-related nephrotoxicity and the recently described multicenter studies. Several factors have been reported as biomarkers of ICIs-irAEs, in this review we speculate on potential biomarkers for ICIs-associated AKI.

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Advancing to the era of cancer immunotherapy

Wang

et al. 2021

Cancer Communications

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Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

Cited by 209 publications

References 52 publications

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

Advancing to the era of cancer immunotherapy

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