Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy

Frontiers in Immunology

Immunology

John Slingerland¹  Marcel van den Brink¹  Roni Shouval²  Alexander Visekruna³  Sarah Staudt⁴  Michael Hudecek⁴  Kai Ziegler-Martin⁴  Maik Luu⁴ 

[1] Department of Immunology, Sloan Kettering Institute, New York, NY, United States;Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States;Department of Medicine, Weill Cornell Medical College, New York, NY, United States;Institute for Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany;Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany;

关键词: microbiome;    immunotherapy;    immunology;    cancer immune cell therapy;    CAR T cell;   

DOI  :  10.3389/fimmu.2023.1269015

 received in 2023-07-28, accepted in 2023-08-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies using chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. The great success in the context of hematologic malignancies has made especially CAR T cell therapy a promising approach capable of achieving long-lasting remission. However, the causalities involved in mediating resistance to treatment or relapse are still barely investigated. Research on T cell exhaustion and dysfunction has drawn attention to host-derived factors that define both the immune and tumor microenvironment (TME) crucially influencing efficacy and toxicity of cellular immunotherapy. The microbiome, as one of the most complex host factors, has become a central topic of investigations due to its ability to impact on health and disease. Recent findings support the hypothesis that commensal bacteria and particularly microbiota-derived metabolites educate and modulate host immunity and TME, thereby contributing to the response to cancer immunotherapy. Hence, the composition of microbial strains as well as their soluble messengers are considered to have predictive value regarding CAR T cell efficacy and toxicity. The diversity of mechanisms underlying both beneficial and detrimental effects of microbiota comprise various epigenetic, metabolic and signaling-related pathways that have the potential to be exploited for the improvement of CAR T cell function. In this review, we will discuss the recent findings in the field of microbiome-cancer interaction, especially with respect to new trajectories that commensal factors can offer to advance cellular immunotherapy.

【 授权许可】

Unknown   
Copyright © 2023 Staudt, Ziegler-Martin, Visekruna, Slingerland, Shouval, Hudecek, van den Brink and Luu