The intimate relationship between gut microbiota and cancer immunotherapy

ABSTRACT Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.

[1]  L. Zitvogel,et al.  The impact of the intestinal microbiota in therapeutic responses against cancer. , 2018, Comptes rendus biologies.

[2]  J. Szustakowski,et al.  Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden , 2018, The New England journal of medicine.

[3]  Stephen Broderick,et al.  Neoadjuvant PD‐1 Blockade in Resectable Lung Cancer , 2018, The New England journal of medicine.

[4]  Laurence Zitvogel,et al.  Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors , 2018, Science.

[5]  E. Le Chatelier,et al.  Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients , 2018, Science.

[6]  Riyue Bao,et al.  The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients , 2018, Science.

[7]  Laurence Zitvogel,et al.  The immune contexture in cancer prognosis and treatment , 2017, Nature Reviews Clinical Oncology.

[8]  L. Zitvogel,et al.  Nutrition, inflammation and cancer , 2017, Nature Immunology.

[9]  M. Socinski,et al.  First‐Line Nivolumab in Stage IV or Recurrent Non–Small‐Cell Lung Cancer , 2017, The New England journal of medicine.

[10]  A. Eggermont,et al.  Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  L. Zitvogel,et al.  Anticancer effects of the microbiome and its products , 2017, Nature Reviews Microbiology.

[12]  Y. Shentu,et al.  Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. , 2016, The New England journal of medicine.

[13]  F. Ginhoux,et al.  Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota , 2015, Science.

[14]  Jason B. Williams,et al.  Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy , 2015, Science.

[15]  A. Ravaud,et al.  Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. , 2015, The New England journal of medicine.

[16]  D. Pardoll.  Cancer and the Immune System: Basic Concepts and Targets for Intervention. , 2015, Seminars in oncology.

[17]  T. Gajewski,et al.  Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity , 2015, Nature.

[18]  Martin L. Miller,et al.  Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer , 2015, Science.

[19]  R. Guigó,et al.  Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. , 2010, Genome research.

[20]  W. M. Vos,et al.  Intestinal Integrity and Akkermansia muciniphila, a Mucin-Degrading Member of the Intestinal Microbiota Present in Infants, Adults, and the Elderly , 2007, Applied and Environmental Microbiology.