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High intratumoral plasma cells content in primary prostate cancer defines a subset of tumors with potential susceptibility to immune-based treatments

Prostate Cancer and Prostatic Diseases volume 26, pages 105–112 (2023)Cite this article

Subjects

Abstract

Background

Data on advanced prostate cancer (PCa) suggest more prior systemic therapies might reduce tumor immune responsiveness. In treatment-naïve primary PCa, recent work correlated intratumoral plasma cell content with enhanced tumor immune-responsiveness. We sought to identify features of localized PCa at a high risk of recurrence following local treatment with high plasma cell content to help focus future immune-based neoadjuvant trials.

Methods

We performed retrospective analyses of molecular profiles from three independent cohorts of over 1300 prostate tumors. We used Wilcoxon Rank Sum to compare molecular pathways between tumors with high and low intratumoral plasma cell content and multivariable Cox proportional hazards regression analyses to assess metastasis-free survival.

Results

We validated an expression-based signature for intratumoral plasma cell content in 113 primary prostate tumors with both RNA-expression data and digital image quantification of CD138+ cells (plasma cell marker) based on immunohistochemisty. The signature showed castration-resistant tumors (n = 101) with more prior systemic therapies contained lower plasma cell content. In high-grade primary PCa, tumors with high plasma cell content were associated with increased predicted response to immunotherapy and decreased response to androgen-deprivation therapy. Master regulator analyses identified upregulated transcription factors implicated in immune (e.g. SKAP1, IL-16, and HCLS1), and B-cell activity (e.g. VAV1, SP140, and FLI-1) in plasma cell-high tumors. Master regulators overactivated in tumors with low plasma cell content were associated with shorter metastasis-free survival following radical prostatectomy.

Conclusions

Markers of plasma cell activity might be leveraged to augment clinical trial targeting and selection and better understand the potential for immune-based treatments in patients with PCa at a high risk of recurrence following local treatment.

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Fig. 1: Immunohistochemistry validation of the plasma cell signature.
The alternative text for this image may have been generated using AI.
Fig. 2: Plasma cell content in mCRPC.
The alternative text for this image may have been generated using AI.
Fig. 3: Expression-based biomarkers in high-grade localized prostate cancer based on plasma cell content.
The alternative text for this image may have been generated using AI.
Fig. 4: Immune pathways in high-grade localized prostate cancer based on plasma cell content.
The alternative text for this image may have been generated using AI.
Fig. 5: Master regulators in primary prostate cancer with high plasma cell content.
The alternative text for this image may have been generated using AI.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported in part by the National Institutes of Health grants 5U01CA196390 (EMS) and R01LM013236 (AM), the Prostate Cancer Foundation (EMS), Department of Defense grant W81XWH-15-1-0661 (EMS and TLL), American Cancer Society grant RSG-21-023-01-TBG (AM, EMS), and New Jersey Commission on Cancer Research grant COCR21RBG00 (AM).

Author information

Authors and Affiliations

  1. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Adam B. Weiner, Mitali Kini & Edward M. Schaeffer

  2. Department of Biomedical and Health Informatics, School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ, USA

    Christina Y. Yu & Antonina Mitrofanova

  3. Veracyte, Inc, San Diego, CA, USA

    Yang Liu & Elai Davicioni

  4. Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA

    Antonina Mitrofanova

  5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Tamara L. Lotan

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  1. Adam B. Weiner
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Contributions

Conception and design: ABW, MD; ED, PhD; AM, PhD; TLL, MD; EMS, MD, PhD. Acquisition of data: ABW, MD; YL, PhD; ED, PhD; TLL, MD; EMS, MD, PhD. Analysis and interpretation of data: ABW, MD; CYY, PhD; YL, PhD. Drafting of Manuscript: ABW, MD; CYY, PhD; MK, MD; YL, PhD; ED, PhD; AM, PhD; TLL, MD; EMS, MD, PhD. Critical Revision of the manuscript for important intellectual content: ABW, MD; ED, PhD; AM, PhD; TLL, MD; EMS, MD, PhD. Statistical analysis: ABW, MD; CYY, PhD. Obtaining funding: AM, PhD; TLL, MD; EMS, MD, PhD. Administrative, technical, or material support: AM, PhD; TLL, MD; EMS, MD, PhD. Supervision: ED, PhD; AM, PhD; TLL, MD; EMS, MD, PhD. Other: none

Corresponding author

Correspondence to Edward M. Schaeffer.

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Competing interests

YL and ED are employees of Veracyte, Inc. The remaining authors declare no potential conflicts of interest.

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The study was performed in accordance with the Declaration of Helsinki.

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Weiner, A.B., Yu, C.Y., Kini, M. et al. High intratumoral plasma cells content in primary prostate cancer defines a subset of tumors with potential susceptibility to immune-based treatments. Prostate Cancer Prostatic Dis 26, 105–112 (2023). https://doi.org/10.1038/s41391-022-00547-0

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