How Could Antibiotics, Probiotics, and Corticoids Modify Microbiota and Its Influence in Cancer Immune Checkpoint Inhibitors: A Review

Cruellas, Mara; Yubero, A.; Zapata, Mario; Gálvez, Eva M.; Gascón, Marta; Isla, Dolores; Lastra, Rodrigo Pimienta; Martínez-Lostao, Luis; Ocáriz, Maitane; Pardo, Julián; Ramírez, Ariel; Sesma, Andrea; Torres-Ramón, Irene; Paño, José Ramón

doi:10.1128/iai.00665-20

Cited by 8 publications

(7 citation statements)

References 45 publications

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“…In chemotherapy regimens containing cytotoxic agents such as platinum, pemetrexed and taxanes, which are the standard treatments for lung cancer, corticosteroids are commonly prescribed as binding pre-treatment for antiemetic and antiallergy purposes. The baseline or early use of corticosteroids at the time of initiating ICI therapy could blunt a proliferative burst of CD8-positive T cells, which are otherwise needed for the ICI therapeutic response, thus affecting the efficacy and toxicity ( 72 , 73 ). In addition, corticosteroids are recommended immunosuppressive agents for various mild-to-severe irAEs such as pneumonitis, colitis, hepatitis, thyroiditis, rash, etc.…”

Section: Discussionmentioning

confidence: 99%

A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

Yan

Cui

et al. 2021

Front. Immunol.

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BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650

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Section: Discussionmentioning

confidence: 99%

A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

Yan

Cui

et al. 2021

Front. Immunol.

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“…Regarding concomitant treatments, several studies have examined the in uence of the use of proton pump inhibitors, antibiotics, or corticosteroids, among others, on the e cacy of immunotherapy. Most associate the use of these treatments with shorter survival and a poorer treatment response (17,23,(34)(35)(36)(37)(38)). An illustrative instance of this phenomenon is the retrospective review conducted by Tinsley et al In their cohort of 291 patients, a subset of 92 received antibiotics, and they exhibited both a reduced PFS and OS in comparison to those who did not receive it (median OS 10.4 months vs. 21.7 months) (39).…”

Section: Discussionmentioning

confidence: 99%

“…The particularities of the gut microbiota between ICI responders and non-responders have previously been reported (11)(12)(13). In addition, the impact of concomitant treatments, such as antibiotics or corticosteroids, in the microbiota composition and nally in the ICI response has been poorly evaluated, despite the current evidence suggesting their implication in the loss of gut microbiota diversity (4,(14)(15)(16)(17). Also, a relationship between immune-related adverse events (IrAEs) and ICI response has been proposed, again without any useful marker for predicting it.…”

Section: Introductionmentioning

confidence: 99%

Impact of Antibiotics, Corticosteroids, and Microbiota on Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer

Zapata-García,

Moratiel,

Isla

et al. 2024

Preprint

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Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.

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“…B. breve was found to be significantly higher in patients who had a better PFS than those who did not, among a cohort of Chinese NSCLC patients treated with anti-PD-1, suggesting its presence as a potential indicative biomarker for better prognosis [73]. Certain other species and genera, such as A. muciniphila, Clostridiales, and Ruminococcaceae, are involved in reversing immunosuppression by improving the gut barrier and thus preventing leaky gut [74]. Four retrospective analyses were performed in Japan between 2020 and 2022 on NSCLC patients undergoing ICI therapy in which some of the patients were administered probiotics.…”

Section: Probioticsmentioning

confidence: 99%

The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer

Duttagupta,

Hakozaki,

Routy

et al. 2023

Current Oncology

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The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients.

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How Could Antibiotics, Probiotics, and Corticoids Modify Microbiota and Its Influence in Cancer Immune Checkpoint Inhibitors: A Review

Cited by 8 publications

References 45 publications

A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

Impact of Antibiotics, Corticosteroids, and Microbiota on Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer

The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer

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