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Evaluation of cancer testis antigen (CT10, PRAME) and MHC I expression in high-grade urothelial carcinoma of the bladder

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Abstract

Immunotherapeutic strategies are increasingly used in the treatment of a number of malignancies including high-grade urothelial carcinoma (HGUC) of the bladder. Because of this, detailed and accurate assessment of the tumor immune microenvironment is paramount. In this study, we aimed to correlate the composition of the tumor immune microenvironment with oncologic outcome and the expression of two cancer testis antigens (CTAs), CT10 and PRAME, potential cancer vaccine targets, as well as major histocompatibility complex I (MHC I), a molecule associated with tumor immune escape and resistance to immunotherapy. Triplicate tissue microarrays (TMAs) were constructed using 207 cases of HGUC of the bladder. Oncologic outcome data was gathered for each case. Consecutive sections from the TMA blocks were stained with CD3, CD4, CD8, FOXP3, PD1, PD-L1, CT10, PRAME, and MHC I. Twenty-one percent and 15% of cases expressed CT10 and PRAME, respectively. Eighty-eight percent of cases showed absent or decreased MHC I expression. CT10-expressing tumors showed a significantly worse disease specific survival (p = 0.007, hazard ratio 2.245, confidence interval 1.223–4.122). CT10, PRAME, and MHC I expression significantly correlated with other some immune parameters. CT10 and PRAME are expressed in a subset of HGUC and CTA and MHC I expression correlate with a number of important immune parameters. Together, these findings highlight the potential for exploring novel immune therapeutic strategies in HGUC. Additional studies evaluating the clinical relevance of these findings are warranted.

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Acknowledgments

CT10, PRAME, and MHC I immunohistochemical staining was performed in the Department of Pathology, Memorial Sloan Kettering Cancer Center in New York, NY, USA. The SP263 antibody was purchased using a Sunnybrook Health Sciences Centre departmental Educational Grant courtesy of Astra Zeneca.

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Authors and Affiliations

  1. Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Anjelica Hodgson & Michelle R. Downes

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Toronto, ON, Canada

    Anjelica Hodgson & Michelle R. Downes

  3. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA

    Achim A. Jungbluth, Nora Katabi & Bin Xu

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  1. Anjelica Hodgson
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  2. Achim A. Jungbluth
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  3. Nora Katabi
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  4. Bin Xu
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  5. Michelle R. Downes
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Contributions

Drs. Downes and Xu conceived and designed the study. Drs. Hodgson, Xu, and Downes gathered the data. Drs. Hodgson, Katabi, Jungbluth, Xu, and Downes reviewed and interpreted the data. Dr. Xu performed the statistical analysis. Drs. Hodgson, Katabi, Jungbluth, Xu, and Downes contributed to drafting and review of the manuscript as well as approval of the final version. Dr. Downes takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Corresponding author

Correspondence to Michelle R. Downes.

Ethics declarations

This project was approved by the Research Ethics Board at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada (REB 187-2016).

Conflict of interest

Dr. Downes has received compensation from Hoffman – La Roche and Astra Zeneca for participating on advisory boards and honoraria from Astra Zeneca.

Dr. Xu has received honoraria from Merck.

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Hodgson, A., Jungbluth, A.A., Katabi, N. et al. Evaluation of cancer testis antigen (CT10, PRAME) and MHC I expression in high-grade urothelial carcinoma of the bladder. Virchows Arch 476, 535–542 (2020). https://doi.org/10.1007/s00428-019-02661-2

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