In contrast to conventional tumor cell-targeting dendritic cell (DC) vaccines, Hu, Shi, and Zhao et al. explored the clinical potential of a therapeutic vaccine loaded with the gut commensal Bacteroides fragilis (DC-Bf). DC-Bf significantly enhanced infiltration of TILs and activation of diverse, cross-reactive CD8+ T cells that recognized and killed tumor cells while decreasing Tregs and immunosuppressive TAMs in the TIME. DC-Bf significantly enhanced the efficacy of anti-PD-1 via an IL-12-driven CD8+ T cell-dependent mechanism in both primary tumor and metastasis models, suggesting translational potential as an off-the-shelf cancer vaccine.
Contributed by Katherine Turner
(1) Hu S (2) Shi G (3) Zhao J (4) Long X (5) Tang L (6) Qi Z (7) Xu X (8) Cheng P (9) Liu J
In contrast to conventional tumor cell-targeting dendritic cell (DC) vaccines, Hu, Shi, and Zhao et al. explored the clinical potential of a therapeutic vaccine loaded with the gut commensal Bacteroides fragilis (DC-Bf). DC-Bf significantly enhanced infiltration of TILs and activation of diverse, cross-reactive CD8+ T cells that recognized and killed tumor cells while decreasing Tregs and immunosuppressive TAMs in the TIME. DC-Bf significantly enhanced the efficacy of anti-PD-1 via an IL-12-driven CD8+ T cell-dependent mechanism in both primary tumor and metastasis models, suggesting translational potential as an off-the-shelf cancer vaccine.
Contributed by Katherine Turner
ABSTRACT: The gut microbiome profoundly influences the clinical benefits of antitumor immunotherapy. Although various gut microbiota have been shown to enhance immunotherapy, their clinical application remains unexplored. In this study, a dendritic cell (DC) vaccine loaded with the gut commensal Bacteroides fragilis (DC-Bf) was used as a therapeutic cancer vaccine. DC-Bf elicited T cell responses that recognize both B. fragilis and tumor cells, primarily via major histocompatibility complex-I-mediated cross-presentation of B. fragilis antigens to prime CD8(+) T cells. DC-Bf treatment increased CD8(+) T cell infiltration and activation, expanded the diversity of the T cell receptor repertoire, and reduced the proportion of regulatory T cells and M2-type tumor-associated macrophages, thereby improving the immunosuppressive tumor microenvironment. In multiple tumor-bearing models, DC-Bf enhanced the therapeutic activity of programmed cell death protein 1 inhibitors by inducing interleukin-12-driven, CD8(+) T cell-dependent antitumor immune responses. This study confirms the potential of using bacteria-loaded DCs to augment immunotherapy efficacy and provides a new perspective for the clinical application of the gut microbiome. Targeting the gut microbiota holds promise as a novel avenue for developing antitumor vaccines.
Author Info:
(1) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (2) Department of Biotherapy, Ca
ncer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (3) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (4) Department of Oncology, West China Hospital, Sichuan University, Sichuan University West China Hospital Guang'an Hospital, Guang'an People's Hospital, Guang'an 638000, China. (5) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (6) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (7) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. (8) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: ping.cheng@foxmail.com. (9) Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: liujiyan1972@163.com.
Citation: Mol Ther 2026 Nov 4 34:6294-6311 Epub08/13/2026
