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

• Published in: Virchows Archiv : an international journal of pathology 2020-04, Vol.476 (4), p.535-542
• Main Authors: Hodgson, Anjelica, Jungbluth, Achim A., Katabi, Nora, Xu, Bin, Downes, Michelle R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Biomarkers, Tumor - immunology; Bladder; Bladder cancer; Cancer; Cancer vaccines; Carcinoma, Transitional Cell - classification; Carcinoma, Transitional Cell - immunology; CD3 antigen; CD4 antigen; CD8 antigen; Confidence intervals; Correlation analysis; Female; Foxp3 protein; Humans; Immunotherapy; Major histocompatibility complex; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Proteins - metabolism; Original Article; Parameters; Pathology; PD-1 protein; PD-L1 protein; Tumor Microenvironment - immunology; Tumors; Urinary Bladder - immunology; Urinary Bladder - metabolism; Urologic Neoplasms - immunology; Urologic Neoplasms - pathology; Urothelial carcinoma
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-019-02661-2

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.