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

Overview

Journal Curr Oncol

Publisher MDPI

Specialty Oncology

Date 2023 Nov 24

PMID 37999101

Authors

Sreya Duttagupta

Taiki Hakozaki

Bertrand Routy

Meriem Messaoudene

Affiliations

Soon will be listed here.

Abstract

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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References

Boesch M, Baty F, Albrich W, Flatz L, Rodriguez R, Rothschild S . Local tumor microbial signatures and response to checkpoint blockade in non-small cell lung cancer. Oncoimmunology. 2021; 10(1):1988403. PMC: 8667931. DOI: 10.1080/2162402X.2021.1988403. View

Huang J, Zheng X, Kang W, Hao H, Mao Y, Zhang H . Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer. Front Immunol. 2022; 13:874922. PMC: 9336524. DOI: 10.3389/fimmu.2022.874922. View

Song P, Yang D, Wang H, Cui X, Si X, Zhang X . Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients. Thorac Cancer. 2020; 11(6):1621-1632. PMC: 7262920. DOI: 10.1111/1759-7714.13442. View

Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M . The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018; 359(6371):104-108. PMC: 6707353. DOI: 10.1126/science.aao3290. View

Spreafico A, Heirali A, Araujo D, Tan T, Oliva M, Schneeberger P . First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial). Ann Oncol. 2023; 34(6):520-530. DOI: 10.1016/j.annonc.2023.02.011. View

Hakozaki T, Richard C, Elkrief A, Hosomi Y, Benlaifaoui M, Mimpen I . The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non-Small Cell Lung Cancer. Cancer Immunol Res. 2020; 8(10):1243-1250. DOI: 10.1158/2326-6066.CIR-20-0196. View

Davis C . The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016; 51(4):167-174. PMC: 5082693. DOI: 10.1097/NT.0000000000000167. View

Zhang X, Li H, Lv X, Hu L, Li W, Zi M . Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors. Life (Basel). 2022; 12(3). PMC: 8951256. DOI: 10.3390/life12030409. View

Mei T, Yang X, Yu M, Tian X, Deng Q, Chen X . Impact of antibiotic use before definitive concurrent chemoradiation in patients with locally advanced non-small cell lung cancer. Strahlenther Onkol. 2022; 199(7):645-657. DOI: 10.1007/s00066-022-02027-9. View

10.

Huemer F, Rinnerthaler G, Westphal T, Hackl H, Hutarew G, Gampenrieder S . Impact of antibiotic treatment on immune-checkpoint blockade efficacy in advanced non-squamous non-small cell lung cancer. Oncotarget. 2018; 9(23):16512-16520. PMC: 5893258. DOI: 10.18632/oncotarget.24751. View

11.

Mino-Kenudson M, Schalper K, Cooper W, Dacic S, Hirsch F, Jain D . Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee. J Thorac Oncol. 2022; 17(12):1335-1354. DOI: 10.1016/j.jtho.2022.09.109. View

12.

Derosa L, Routy B, Thomas A, Iebba V, Zalcman G, Friard S . Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med. 2022; 28(2):315-324. PMC: 9330544. DOI: 10.1038/s41591-021-01655-5. View

13.

Baruch E, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L . Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2020; 371(6529):602-609. DOI: 10.1126/science.abb5920. View

14.

Takada K, Buti S, Bersanelli M, Shimokawa M, Takamori S, Matsubara T . Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade. Eur J Cancer. 2022; 172:199-208. DOI: 10.1016/j.ejca.2022.06.002. View

15.

Modi S, Collins J, Relman D . Antibiotics and the gut microbiota. J Clin Invest. 2014; 124(10):4212-8. PMC: 4191029. DOI: 10.1172/JCI72333. View

16.

Nomura M, Nagatomo R, Doi K, Shimizu J, Baba K, Saito T . Association of Short-Chain Fatty Acids in the Gut Microbiome With Clinical Response to Treatment With Nivolumab or Pembrolizumab in Patients With Solid Cancer Tumors. JAMA Netw Open. 2020; 3(4):e202895. PMC: 7163404. DOI: 10.1001/jamanetworkopen.2020.2895. View

17.

Derosa L, Routy B, Desilets A, Daillere R, Terrisse S, Kroemer G . Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?. Cancer Discov. 2021; 11(10):2396-2412. DOI: 10.1158/2159-8290.CD-21-0236. View

18.

Ouaknine Krief J, Helly de Tauriers P, Dumenil C, Neveux N, Dumoulin J, Giraud V . Role of antibiotic use, plasma citrulline and blood microbiome in advanced non-small cell lung cancer patients treated with nivolumab. J Immunother Cancer. 2019; 7(1):176. PMC: 6621972. DOI: 10.1186/s40425-019-0658-1. View

19.

Paz-Ares L, Ciuleanu T, Cobo M, Schenker M, Zurawski B, Menezes J . First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(2):198-211. DOI: 10.1016/S1470-2045(20)30641-0. View

20.

Ma S, Yu H, Khan M, Gill J, Santhosh S, Chatterjee U . Evaluation of Optimal Threshold of Neutrophil-Lymphocyte Ratio and Its Association With Survival Outcomes Among Patients With Head and Neck Cancer. JAMA Netw Open. 2022; 5(4):e227567. PMC: 9012962. DOI: 10.1001/jamanetworkopen.2022.7567. View