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Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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Abstract

Background

A growing number of studies have shown that in addition to adaptive immune cells such as CD8 + T cells and CD4 + T cells, various other cellular components within prostate cancer (PCa) tumor microenvironment (TME), mainly tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs), have been increasingly recognized as important modulators of tumor progression and promising therapeutic targets.

Objective

In this review, we aim to delineate the mechanisms by which TAMs, CAFs and MDSCs interact with PCa cells in the TME, summarize the therapeutic advancements targeting these cells and discuss potential new therapeutic avenues.

Methods

We searched PubMed for relevant studies published through December 10 2023 on TAMs, CAFs and MDSCs in PCa.

Results

TAMs, CAFs and MDSCs play a critical role in the tumorigenesis, progression, and metastasis of PCa. Moreover, they substantially mediate therapeutic resistance against conventional treatments including anti-androgen therapy, chemotherapy, and immunotherapy. Therapeutic interventions targeting these cellular components have demonstrated promising effects in preclinical models and several clinical trials for PCa, when administrated alone, or combined with other anti-cancer therapies. However, the lack of reliable biomarkers for patient selection and incomplete understanding of the mechanisms underlying the interactions between these cellular components and PCa cells hinder their clinical translation and utility.

Conclusion

New therapeutic strategies targeting TAMs, CAFs, and MDSCs in PCa hold promising prospects. Future research endeavors should focus on a more comprehensive exploration of the specific mechanisms by which these cells contribute to PCa, aiming to identify additional drug targets and conduct more clinical trials to validate the safety and efficacy of these treatment strategies.

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Fig. 1: The roles of TAMs, CAFs and MDSCs within the TME of PCa and therapeutic strategies targeting these cells.

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Acknowledgements

This work was supported by Oriental Scholar Professorship, Shanghai Municipal Commission of Education, China; National Nature Science Foundation of China (82172621, 81972375); Shanghai Medical Innovation Research Special Project (21Y11904300); Shanghai Shenkang Research Physician Innovation and Transformation Ability Training Project (SHDC2022CRD035); General Program of Beijing Xisike Clinical Oncology Research Foundation (Y-MSDZD2021-0230, Y-2019AZMS-0012); Chinese Anti-Cancer Association - Hengrui PARP Inhibitor Cancer Research Foundation; Shanghai Academic/Technology Research Leader (23XD1420600); Research Project on Clinical Studies of Innovative Drugs after Market Launch (WKZX2023CX100001).

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Authors and Affiliations

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Bangwei Fang, Xiaomeng Li, Yu Wei, Dingwei Ye & Yao Zhu

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

    Bangwei Fang, Xiaomeng Li, Yu Wei, Dingwei Ye & Yao Zhu

  3. Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China

    Bangwei Fang, Xiaomeng Li, Yu Wei, Dingwei Ye & Yao Zhu

  4. Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China

    Ying Lu & Gonghong Wei

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Conceptualization, YZ, DY, and BF; Writing—original draft preparation, BF, XL and YW; Writing—review and editing, YL, DY, YZ and HW; Funding acquisition, YZ All authors have read and agreed to the published version of the manuscript.

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Fang, B., Lu, Y., Li, X. et al. Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00825-z

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