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Antibiotic-associated dysbiosis is linked to poorer ICI response and reduced overall survival among patients receiving antibiotics before treatment. Preclinical studies explore probiotics, prebiotics, diet, and fecal microbiota transplantation to beneficially reshape the microbiome and improve ICI efficacy. Clinical trials are underway with encouraging early results. The review summarizes recent evidence supporting the gut microbiome as both a biomarker and an adjuvant strategy for NSCLC ICI 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\nLung Cancer  \nSreya Duttagupta 1, Taiki Hakozaki 1,2, Bertrand Routy 1,3,* and Meriem Messaoudene 1, *  \nCitation: Duttagupta, S.; Hakozaki, T.; Routy, B.; Messaoudene, M. The Gut Microbiome from a Biomarker toa Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer. Curr. Oncol. 2023, 30, 9406–9427. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol30110681](10.3390/curroncol30110681)  \nReceived: 2 August 2023  \nRevised: 19 August 2023  \nAccepted: 20 August 2023  \nPublished: 24 October 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 University of Montreal Research Centre (CRCHUM), Montreal, QC H2X 0A9, Canada; [sreya.duttagupta@umontreal.ca](sreya.duttagupta@umontreal.ca) (S.D.); [t-hakozaki@akane.waseda.jp](t-hakozaki@akane.waseda.jp) (T.H.)  \n2 Graduate School of Advanced Science and Engineering, Faculty of Science and Engineering, Waseda University, Tokyo 169-8050, Japan  \n3 Hematology-Oncology Division, Department of Medicine, University of Montreal Healthcare Centre, Montreal, QC H2X 3E4, Canada  \n* [Correspondence: bertrand.routy@umontreal.ca](Correspondence: bertrand.routy@umontreal.ca) (B.R.); [meriem.messaoudene@umontreal.ca](meriem.messaoudene@umontreal.ca) (M.M.)  \nAbstract: 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 anadjuvant therapy to ICIs in NSCLC patients.  \nKeywords: non-small cell lung cancer; immune checkpoint inhibitors; gut microbiome; antibiotics; probiotics; prebiotics; polyphenols; fecal microbiota transplantation; diet  \n1. Introduction  \nAmong all the molecular pathways involved in the development of a neoplasm, the inherent ability of cancer cells to escape immune response is the most important factor in their growth and has simultaneously revolutionized cancer treatment [1] . The advent of immune checkpoint inhibitors (ICIs) with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) has provided unprecedented efficacy gains in numerous cancers including non-small cell lung cancer (NSCLC) . For patients with high PD-L1 when anti-PD-1 is used as a first-line monotherapy, median overall survival (OS) has nearly doubled (26.3 months vs. 13.4 months), and the 5-year survival has also increased (31.9% vs. 16.3%) in comparison to conventional cytotoxic chemotherapy. Even for the population with low or negative PD-L1, the combination of anti-PD-L1 and chemotherapy yielded a median OS of over 20 months and a 5","cbCainIHLrEFyQC2","https://ap.wps.com/l/cbCainIHLrEFyQC2","pdf",868864,22,"English","# Introduction\n## Immune checkpoint inhibitors and response variability\n## Gut microbiome and immune system homeostasis\n# Role of microbiome composition as biomarker\n## Antibiotic-associated dysbiosis and survival impact\n# Therapeutic strategies to modulate the gut microbiome\n## Probiotics, prebiotics, diet\n## Fecal microbiota transplantation","[{\"question\":\"How does the gut microbiome influence immunotherapy outcomes in lung cancer?\",\"answer\":\"The gut microbiome affects host immune system homeostasis and has been linked to responses to immune checkpoint inhibitor therapy in non-small cell lung cancer, including immune-related adverse events.\"},{\"question\":\"What is the relationship between antibiotics and ICI response?\",\"answer\":\"Antibiotic-related dysbiosis has been consistently associated with a deleterious impact on ICI response and shorter overall survival in patients who received antibiotics before ICI initiation.\"},{\"question\":\"Which interventions are discussed to improve ICI efficacy by modifying the microbiome?\",\"answer\":\"The review describes strategies including probiotics, prebiotics, diet, and fecal microbiota transplantation, aimed at shifting the microbiome to enhance ICI efficacy.\"}]","The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer | PDF",1790247490,55]