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Cellular and Molecular Biology

Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome

British Journal of Cancer volume 128, pages 1466–1477 (2023)Cite this article

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A Correction to this article was published on 20 March 2023

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Abstract

Background

The clinical significance and immune correlation of CD103+ cells in prostate cancer (PCa) remain explored.

Methods

In total, 1080 patients with PCa underwent radical prostatectomy from three cohorts were enrolled for retrospective analysis. Tumour microarrays were constructed and fresh tumour samples were analysed by flow cytometry.

Results

High CD103+ cell infiltration correlated with reduced biochemical recurrence (BCR)-free survival in PCa. Adjuvant hormone therapy (HT) prolonged the BCR-free survival for high-risk node-negative diseases with CD103+ cell abundance. CD103+ cell infiltration correlated with less cytotoxic expression and increased infiltration of CD8+ and CD4+ T cells, M1 macrophages and mast cells in PCa. Intratumoral CD8+ T cell was the predominant source of CD103, and the CD103+ subset of CD8+ T cells was featured with high IL-10, PD-1 and CTLA-4 expression. Tumour-infiltrating CD103+ CD8+ T cells exerted anti-tumour function when treated with HT ex vivo.

Discussion

CD103+ cell infiltration predicted BCR-free survival and response to adjuvant HT in PCa. CD103+ cell infiltration correlated with an enriched but immune-evasive immune landscape. The study supported a model that CD103 expression conferred negative prognostic impact and immunosuppressive function to tumour-infiltrating CD8+ T cells, while the CD103+ CD8+ T cells exhibited a powerful anti-tumour immunity with response to HT.

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Fig. 1: Prevalence of tumour-infiltrating CD103+ cells correlated with tumour progression in PCa.
Fig. 2: CD103+ cell infiltration showed prognostic significance in PCa.
Fig. 3: Enrichment of CD103+ cell infiltration was associated with superior response to adjuvant HT in PCa.
Fig. 4: CD103+ cell abundance characterised immune-inflamed PCa with diminished cytotoxicity.
Fig. 5: CD103 characterised CD8+ T cells with immunosuppressive phenotype in PCa.
Fig. 6: PDE models demonstrated the activation of anti-tumour immunity of CD103+ CD8+ T cells with hormone therapy in PCa.

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Data availability

All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author Dr. Jiang upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 81872102, 82002720 and 81802569).

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Author notes

  1. These authors contributed equally: Quan Zhou, Yuxi Ou, Xiyu Dai, Xinan Chen.

Authors and Affiliations

  1. Department of Urology, Huashan Hospital, Fudan University, Shanghai, China

    Quan Zhou, Yuxi Ou, Xiyu Dai, Xinan Chen, Siqi Wu, Wensun Chen, Mengbo Hu, Chen Yang, Limin Zhang & Haowen Jiang

  2. Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China

    Quan Zhou, Yuxi Ou, Xiyu Dai, Xinan Chen, Siqi Wu, Wensun Chen, Mengbo Hu, Chen Yang, Limin Zhang & Haowen Jiang

  3. National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China

    Chen Yang, Limin Zhang & Haowen Jiang

  4. Department of Urology, Jing’an District Central Hospital, Fudan University, Shanghai, China

    Haowen Jiang

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  1. Quan Zhou
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Contributions

QZ, YO, XD and XC for the acquisition of data, analysis and interpretation of the data, statistical analysis and drafting of the manuscript; SW, WC and MH for technical and material support; CY, LZ and HJ for 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 Chen Yang, Limin Zhang or Haowen Jiang.

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Ethics approval and consent to participate

The study was conducted by Huashan Hospital, Fudan University. All tissue-related experiments were in accordance with the regulations of the tissue bank and the study protocol was approved by the Huashan Hospital Institutional Review Board (KY2011-009). The study followed the ethical principles of the Declaration of Helsinki and signed informed consent was obtained from the participants.

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The original online version of this article was revised: There was an error in the scale bar in Figure 4g “Dendritic Cell” (right panel). The scale bar should be “50um”, not “100um”. The error occurred during typesetting.

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Zhou, Q., Ou, Y., Dai, X. et al. Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome. Br J Cancer 128, 1466–1477 (2023). https://doi.org/10.1038/s41416-023-02183-4

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