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Stromal Tumor-Associated Macrophage Infiltration Predicts Poor Clinical Outcomes in Muscle-Invasive Bladder Cancer Patients

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC).

Patients and Methods

This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value.

Results

Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006–1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition.

Conclusions

Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.

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Data Availability Statement

All data relevant to the results presented herein are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Dr. Lingli Chen (Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China) and Dr. Yunyi Kong (Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China) for their excellent pathological technology help.

Funding

This study was funded by grants from National Natural Science Foundation of China (31770851, 81872082, 82002670, 82103408), Shanghai Municipal Natural Science Foundation (19ZR1431800), Shanghai Sailing Program (18YF1404500, 21YF1407000), Shanghai Municipal Commission of Health and Family Planning Program (201840168), and Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation (YJYQ201802). All these study sponsors had no role in the study design, or in the collection, analysis, and interpretation of data.

Author information

Author notes

  1. Shengming **, Han Zeng, Zhaopei Liu and Kaifeng ** have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China

    Shengming ** MD, Yuan Chang MD & Yu Zhu PhD

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Shengming ** MD, Yuan Chang MD & Yu Zhu PhD

  3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Han Zeng MD, Zhaopei Liu MD, Kaifeng ** MD, Chunnan Liu MD, Sen Yan MD, Yanze Yu MD, Runze You MD, Hongyi Zhang MD & Jiejie Xu MD, PhD

  4. Department of Urology, Rui** Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Le Xu PhD

  5. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China

    Zewei Wang MD

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  1. Shengming ** MD
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  2. Han Zeng MD
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Contributions

SJ, HZ, ZL, and KJ: acquisition of data, analysis and interpretation of data, statistical analysis, and drafting of the manuscript; CL, SY, YY, RY, HZ, JZ, YC, and LX: technical and material support; JX, ZW, and YZ: study concept and design, analysis, and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zewei Wang MD or Yu Zhu PhD.

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Disclosure

The authors declare no potential conflicts of interest.

Ethics Approval and Consent to Participate

The study followed the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of Fudan University Shanghai Cancer Center (No. 050432-4-1212B). Signed informed consent was acquired from each patient.

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All authors provide their consent for publication.

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**, S., Zeng, H., Liu, Z. et al. Stromal Tumor-Associated Macrophage Infiltration Predicts Poor Clinical Outcomes in Muscle-Invasive Bladder Cancer Patients. Ann Surg Oncol 29, 2495–2503 (2022). https://doi.org/10.1245/s10434-021-11155-y

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  • DOI: https://doi.org/10.1245/s10434-021-11155-y

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