Reprogramming innate immune memory in bladder cancer: the proposed bone marrow–bladder axis and next-generation BCG-based immunotherapies
5 affiliations
- 1Department of Geriatric, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine
- 2Department of Colorectal and Anal Surgery, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine
- 3Department of Urology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine
- 4Department of General Practice, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine
- 5Department of Emergency, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine
Abstract
Intravesical Bacillus Calmette–Guérin (BCG) remains the standard adjuvant treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), yet the mechanisms underlying its durable clinical benefit and treatment resistance remain incompletely understood. Although BCG has traditionally been regarded as a local immunotherapy, emerging clinical and preclinical evidence suggests that intravesical BCG can induce trained-immunity-associated systemic immune changes, including alterations in circulating innate immune responses and hematopoietic programming. In this Review, we propose the bone marrow–bladder axis as a hypothesis-generating conceptual framework linking local microbial sensing with systemic hematopoietic responses that may contribute to sustained myeloid and adaptive antitumor immunity. Building upon this framework, we further introduce the Failure-to-Train (FTT) model, which proposes that selected immune-training-related mechanisms may contribute to heterogeneous patterns of BCG failure through disruption of productive immune training at distinct stages of the proposed immune-training circuit. Finally, we discuss the implications of this framework for biomarker development, experimental validation and mechanism-guided immunotherapy. By considering systemic immune training as a potential contributor to BCG responses, this Review provides a conceptual framework for investigating treatment response and resistance and for developing testable strategies for next-generation immunotherapy.
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BibTeX
@article{yang2026reprogramming,
title = {{Reprogramming innate immune memory in bladder cancer: the proposed bone marrow–bladder axis and next-generation BCG-based immunotherapies}},
author = {Meng Yang and Yu Guo and Yu-zhao Shen and Yan-Li Sun and Dai-Ju Ma and Yuan-Jia Tang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1945559},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945559/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Reprogramming innate immune memory in bladder cancer: the proposed bone marrow–bladder axis and next-generation BCG-based immunotherapies
AU - Meng Yang
AU - Yu Guo
AU - Yu-zhao Shen
AU - Yan-Li Sun
AU - Dai-Ju Ma
AU - Yuan-Jia Tang
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1945559
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945559/full
AB - Intravesical Bacillus Calmette–Guérin (BCG) remains the standard adjuvant treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), yet the mechanisms underlying its durable clinical benefit and treatment resistance remain incompletely understood. Although BCG has traditionally been regarded as a local immunotherapy, emerging clinical and preclinical evidence suggests that intravesical BCG can induce trained-immunity-associated systemic immune changes, including alterations in circulating innate immune responses and hematopoietic programming. In this Review, we propose the bone marrow–bladder axis as a hypothesis-generating conceptual framework linking local microbial sensing with systemic hematopoietic responses that may contribute to sustained myeloid and adaptive antitumor immunity. Building upon this framework, we further introduce the Failure-to-Train (FTT) model, which proposes that selected immune-training-related mechanisms may contribute to heterogeneous patterns of BCG failure through disruption of productive immune training at distinct stages of the proposed immune-training circuit. Finally, we discuss the implications of this framework for biomarker development, experimental validation and mechanism-guided immunotherapy. By considering systemic immune training as a potential contributor to BCG responses, this Review provides a conceptual framework for investigating treatment response and resistance and for developing testable strategies for next-generation immunotherapy.
SN - 1664-3224
ER -