The Gut Microbiome Drives Endogenous T Cell Activation Following CAR-T Cell Therapy.

Authors

Kejia Hu, Lele Jin, Zidan Feng, Qinru Yu, Xiaohui Si, Lijuan Ding, Yingli Han, Meng Zhu, Ce Shi, Xiangjun Zeng, Kaiting Wang, Jieping Wei, Yuqi Lv, Delin Kong, Lulu Qin, Li Yu, Lixin Wang, Mingming Zhang, Pengxu Qian, Yongxian Hu, Dongrui Wang, He Huang

Published in

Cancer immunology research. Jul 22, 2026. Epub Jul 22, 2026.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has become a promising clinical approach against hematological malignancies, but patients receiving CAR-T cell therapy still presented inconsistent clinical outcomes and are complicated by incomplete tumor eradication. The gut microbiome has shown strong correlation with the therapeutic outcomes of CAR-T cell therapy. However, the underlying mechanism of how gut microbiota affect CAR-T cell therapeutic potency remained undetermined. In this study, we established a syngeneic CD19+ murine lymphoma model which allows for the evaluation of both endogenous immune cells and gut microbiota following CD19-CD28ζ CAR-T therapy. Using single-cell transcriptomic analyses, we report that CAR-T cell infusion led to the activation of peripheral and gut-infiltrating endogenous CD8+ T cells towards an effector-like phenotype. In parallel, 16S RNA sequencing revealed substantial alterations of gut microbiota post-infusion. The composition of gut bacteria was associated with the activation status of endogenous CD8+ T cells and responsiveness to CAR-T therapy. More specifically, we identified gut bacteria strains Turicibacter and Parvibactor as critical determinants towards effective CAR-T treatment. Supplementation of these species of gut bacteria during CAR-T cell therapy led to superior antitumor efficacy. Furthermore, both strains facilitated CAR-T therapy-induced activation of endogenous CD8+ T cells, enhancing their capability to express activation-associated surface markers as well as tumor-lysis potency. In summary, our results demonstrate that gut microbiome plays an essential role in endogenous immune activation after CAR-T therapy and provide specific targets for therapeutic interventions.

PMID:
42485357
Bibliographic data and abstract were imported from PubMed on 23 Jul 2026.

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