Nicholas J Salgia1, Paulo G Bergerot1, Manuel Caitano Maia2, Nazli Dizman1, JoAnn Hsu1, John D Gillece3, Megan Folkerts3, Lauren Reining3, Jeffrey Trent4, Sarah K Highlander5, Sumanta K Pal6. 1. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 2. Centro de Oncologia do Paraná, Curitiba, Brazil. 3. Pathogen and Microbiome Division, Translational Genomics Research Institute North, Flagstaff, AZ, USA. 4. Translational Genomics Research Institute, Phoenix, AZ, USA. 5. Pathogen and Microbiome Division, Translational Genomics Research Institute North, Flagstaff, AZ, USA. Electronic address: shighlander@tgen.org. 6. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Electronic address: spal@coh.org.
Abstract
Preclinical models and early clinical data suggest an interplay between the gut microbiome and response to immunotherapy in solid tumors including metastatic renal cell carcinoma (mRCC). We sought to characterize the stool microbiome of mRCC patients receiving a checkpoint inhibitor (CPI) and to assess treatment-related changes in microbiome composition over the course of CPI therapy. Stool was collected from 31 patients before initiation of nivolumab (77%) or nivolumab plus ipilimumab (23%) therapy, of whom 58% experienced clinical benefit. Greater microbial diversity was associated with clinical benefit from CPI therapy (p = 0.001), and multiple species were associated with clinical benefit or lack thereof. Temporal profiling of the microbiome indicated that the relative abundance of Akkermansia muciniphila increased in patients deriving clinical benefit from CPIs. This study substantiates results from previous CPI-related microbiome profiling studies in mRCC. Temporal changes in microbiome composition suggest potential utility in modulating the microbiome for more successful CPI outcomes. PATIENT SUMMARY: We compared the composition and diversity of the gut microbiome in patients receiving immunotherapy for renal cell carcinoma. We found that higher microbial diversity is associated with better treatment outcomes. Treatment response is characterized by changes in microbial species over the course of treatment.
Preclinical models and early clinical data suggest an interplay between the gut microbiome and response to immunotherapy in solid tumors including metastatic renal cell carcinoma (mRCC). We sought to characterize the stool microbiome of mRCC patients receiving a checkpoint inhibitor (CPI) and to assess treatment-related changes in microbiome composition over the course of CPI therapy. Stool was collected from 31 patients before initiation of nivolumab (77%) or nivolumab plus ipilimumab (23%) therapy, of whom 58% experienced clinical benefit. Greater microbial diversity was associated with clinical benefit from CPI therapy (p = 0.001), and multiple species were associated with clinical benefit or lack thereof. Temporal profiling of the microbiome indicated that the relative abundance of Akkermansia muciniphila increased in patients deriving clinical benefit from CPIs. This study substantiates results from previous CPI-related microbiome profiling studies in mRCC. Temporal changes in microbiome composition suggest potential utility in modulating the microbiome for more successful CPI outcomes. PATIENT SUMMARY: We compared the composition and diversity of the gut microbiome in patients receiving immunotherapy for renal cell carcinoma. We found that higher microbial diversity is associated with better treatment outcomes. Treatment response is characterized by changes in microbial species over the course of treatment.
Authors: Hai Liang; Jay-Hyun Jo; Zhiwei Zhang; Margaret A MacGibeny; Jungmin Han; Diana M Proctor; Monica E Taylor; You Che; Paul Juneau; Andrea B Apolo; John A McCulloch; Diwakar Davar; Hassane M Zarour; Amiran K Dzutsev; Isaac Brownell; Giorgio Trinchieri; James L Gulley; Heidi H Kong Journal: Oncotarget Date: 2022-07-19
Authors: Elizabeth M Park; Manoj Chelvanambi; Neal Bhutiani; Guido Kroemer; Laurence Zitvogel; Jennifer A Wargo Journal: Nat Med Date: 2022-04-19 Impact factor: 87.241