The Pretreatment Tumor Microenvironment Immune Status Determines Bacillus Calmette–Guerin Immunotherapy Response in Early-Stage Bladder Cancer
5 affiliations
- 1Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Gansu Urological Clinical Center, Lanzhou, China.
- 2Department of Pathology, Lanzhou University Second Hospital, Lanzhou, China.
- 3Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, The Legorreta Cancer Center at Brown University, Brown University Health, Providence, Rhode Island.
- 4Department of Surgery (Urology), Brown University Warren Alpert Medical School, The Legorreta Cancer Center at Brown University, Brown University Health, Providence, Rhode Island.
- 5Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Abstract
Bacillus Calmette–Guérin (BCG) is the standard adjuvant therapy for early-stage bladder cancer, based on its immunostimulatory activity. However, more than half of patients experience BCG failure and subsequent recurrence. The heterogeneity of the tumor microenvironment may influence BCG response; however, this relationship is currently not well established. We found that BCG response did not correlate with the number of tumor-infiltrating T cells but was determined by the pretreatment immunosuppressive microenvironment. We identified a subset of cancer-associated fibroblasts characterized by microfibrillar-associated protein 2 (MFAP2+ CAF), which impaired BCG-induced antitumoral immunity by interacting with both individual T cells and tertiary lymphoid structures/lymphoid aggregates. This study also revealed a potential stepwise activation of cancer immune evasion factors based on cross-sectional analysis, from increasing MFAP2+ CAF to activation of programmed cell death ligand 1 and then lymphocyte-activation gene 3 on T cells during early-stage bladder cancer development. These findings have the potential to enable accurate prediction of BCG response. This approach may also be applicable to the investigation of other human cancers.
Related
- Tuberculous discitis following traumatic intravesical Bacillus Calmette-Guérin treatment: illustrative case
- Case Report: Contezolid-containing regimens for disseminated Bacillus Calmette–Guérin disease in three children with primary immunodeficiency
- Physician-modified fenestrated thoracic endovascular aortic repair for a rapidly developing infectious distal aortic arch aneurysm after intravesical bacillus Calmette-Guérin therapy.
- Inflammatory Myofibroblastic Tumor of the Bladder Following Intravesical Bacillus Calmette-Guérin Therapy: A Case Report
- Bladder-Sparing Therapies for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ: An Upper and a Lower Response Group With an Unstable Boundary
BibTeX
@article{guo2026pretreatment,
title = {{The Pretreatment Tumor Microenvironment Immune Status Determines Bacillus Calmette–Guerin Immunotherapy Response in Early-Stage Bladder Cancer}},
author = {Yufeng Guo and Xuezhao Ren and Ze Zhang and Hui Cheng and Jin-Peng Ma and Hong Yan and Qian Niu and Xinyu Zhang and Luyang Zhang and Junqiang Tian and Zhilong Dong and Hanzhang Wang and Liang Cheng and Yong-Jie Lu and Zhiping Wang},
journal = {Cancer Immunology Research},
year = {2026},
month = aug,
doi = {10.1158/2326-6066.cir-25-1445},
url = {https://doi.org/10.1158/2326-6066.cir-25-1445},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The Pretreatment Tumor Microenvironment Immune Status Determines Bacillus Calmette–Guerin Immunotherapy Response in Early-Stage Bladder Cancer
AU - Yufeng Guo
AU - Xuezhao Ren
AU - Ze Zhang
AU - Hui Cheng
AU - Jin-Peng Ma
AU - Hong Yan
AU - Qian Niu
AU - Xinyu Zhang
AU - Luyang Zhang
AU - Junqiang Tian
AU - Zhilong Dong
AU - Hanzhang Wang
AU - Liang Cheng
AU - Yong-Jie Lu
AU - Zhiping Wang
PY - 2026
DA - 2026/08/11
JO - Cancer Immunology Research
DO - 10.1158/2326-6066.cir-25-1445
UR - https://doi.org/10.1158/2326-6066.cir-25-1445
AB - Bacillus Calmette–Guérin (BCG) is the standard adjuvant therapy for early-stage bladder cancer, based on its immunostimulatory activity. However, more than half of patients experience BCG failure and subsequent recurrence. The heterogeneity of the tumor microenvironment may influence BCG response; however, this relationship is currently not well established. We found that BCG response did not correlate with the number of tumor-infiltrating T cells but was determined by the pretreatment immunosuppressive microenvironment. We identified a subset of cancer-associated fibroblasts characterized by microfibrillar-associated protein 2 (MFAP2+ CAF), which impaired BCG-induced antitumoral immunity by interacting with both individual T cells and tertiary lymphoid structures/lymphoid aggregates. This study also revealed a potential stepwise activation of cancer immune evasion factors based on cross-sectional analysis, from increasing MFAP2+ CAF to activation of programmed cell death ligand 1 and then lymphocyte-activation gene 3 on T cells during early-stage bladder cancer development. These findings have the potential to enable accurate prediction of BCG response. This approach may also be applicable to the investigation of other human cancers.
SN - 2326-6066
SN - 2326-6074
ER -