Gut microbiome and CAR-T therapy

• Main Authors: Muhammad Bilal Abid, Nirav N. Shah, Theresa C. Maatman, Parameswaran N. Hari
• Format: Article
• Language: English
• Published: BMC 2019-11-01
• Series: Experimental Hematology & Oncology
• Subjects: Immunotherapy; Immuno-oncology; CAR T-cells; TRUCKs; Gut microbiome; Dysbiosis
• Online Access: http://link.springer.com/article/10.1186/s40164-019-0155-8

Abstract Considerable progress has been made in cancer therapeutics recently with targeted strategies that are efficacious and less toxic. Immunotherapy and chimeric antigen receptor (CAR) T-cells are increasingly being evaluated in a variety of tumors in the relapsed/refractory as well as frontline disease settings, predominantly in hematologic malignancies (HM). Despite impressive outcomes in select patients, there remains significant heterogeneity in clinical response to CAR T-cells. The gut microbiome has emerged as one of the key host factors that could potentially be modulated to enhance responses to immunotherapy. Several recent human studies receiving immunotherapy showed a significantly superior response and survival in patients with the more diverse gut microbiome. Currently, it is unknown if gut microbiota modulates anti-tumor responses to CAR T-cells. Based on molecular and immunological understanding, we hypothesize that strategically manipulating gut microbiota may enhance responses to CAR T-cells. In this review, we further discuss resistance mechanisms to CAR T-cells in HM, potential approaches to overcome resistance by harnessing gut microbiota and other related novel strategies.