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

Sarah Staudt, Kai Ziegler-Martin, Alexander Visekruna, John Slingerland, Roni Shouval, Michael Hudecek, Marcel van den Brink, Maik Luu*

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

Abstract

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.

Original languageEnglish
Article number1269015
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Funding

FundersFunder number
BZKF
Bavarian Center for Cancer Research
Bayerisches Zentrum für Krebsforschung
Starr Cancer Consortium
Susan and Peter Solomon Family Fund
National Institute on AgingP01-AG052359
National Heart, Lung, and Blood InstituteR01-HL164902
National Cancer InstituteP01-CA023766, R01-CA228308, P30 CA008748, R35-CA284024
Lymphoma Foundation
Wilhelm Sander-Stiftung2022.134.1
Horizon 2020 Framework Programme
European Federation of Pharmaceutical Industries and Associations
Parker Institute for Cancer Immunotherapy
Cycle for Survival
Paula and Rodger Riney Foundation
Seres Therapeutics
Deutsche ForschungsgemeinschaftTRR338, TRR 221
Julius-Maximilians-Universität Würzburg
Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum WürzburgS-511
Innovative Medicines Initiative116026

    Keywords

    • CAR T cell
    • cancer immune cell therapy
    • immunology
    • immunotherapy
    • microbiome

    Fingerprint

    Dive into the research topics of 'Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy'. Together they form a unique fingerprint.

    Cite this