Anjelica Hodgson1,2, Stanley K Liu3, Danny Vesprini3, Bin Xu1,2, Michelle R Downes1,2. 1. Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 3. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Abstract
AIMS: Basal and luminal molecular subgroups of muscle-invasive urothelial carcinoma (UC) can be recognised by the use of immunohistochemical markers. Studies have shown that responses to chemotherapy and outcomes differ among these subtypes. High-grade UC of the bladder is an immunogenic neoplasm that induces a substantial intratumoral and peritumoral immune response; the phenotype of infiltrating immune cells may yield prognostic information and predict response to therapy. In this study, we aimed to correlate the immunohistochemical phenotype of high-grade UC with immune microenvironment composition. METHODS AND RESULTS: Two hundred and thirty-five cases of high-grade UC treated with cystectomy were reviewed. Clinicopathological variables for each case were recorded, and disease-free survival at last follow-up was calculated. Invasive front inflammation and tumour-infiltrating lymphocytes were scored for each case. Two hundred and seven cases were used to construct a triplicate-core tissue microarray (TMA), with sections stained for cytokeratin (CK) 5/6 and GATA3. Of the evaluable cases, 167 were designated as luminal (CK5/6- and GATA3+) and 29 as basal (CK5/6+ and GATA3-). Additional sequential TMA sections were stained for CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) (SP263). Basal-subtype tumours showed a trend towards worse disease-specific survival (P = 0.078). There were statistically significant associations between basal subtype and CD8 expression (P = 0.008), PD-1 expression (P = 0.001), and PD-L1 expression (P = 0.014). Lower CD4/CD8 and increased CD8/FOXP3 ratios (P = 0.047 and P = 0.031, respectively) were also identified in the basal-subtype group. CONCLUSIONS: Basal-subtype high-grade UC has an abundance of CD8+ T cells with increased expression of inhibitory markers, indicative of a 'hot' immunophenotype.
AIMS: Basal and luminal molecular subgroups of muscle-invasive urothelial carcinoma (UC) can be recognised by the use of immunohistochemical markers. Studies have shown that responses to chemotherapy and outcomes differ among these subtypes. High-grade UC of the bladder is an immunogenic neoplasm that induces a substantial intratumoral and peritumoral immune response; the phenotype of infiltrating immune cells may yield prognostic information and predict response to therapy. In this study, we aimed to correlate the immunohistochemical phenotype of high-grade UC with immune microenvironment composition. METHODS AND RESULTS: Two hundred and thirty-five cases of high-grade UC treated with cystectomy were reviewed. Clinicopathological variables for each case were recorded, and disease-free survival at last follow-up was calculated. Invasive front inflammation and tumour-infiltrating lymphocytes were scored for each case. Two hundred and seven cases were used to construct a triplicate-core tissue microarray (TMA), with sections stained for cytokeratin (CK) 5/6 and GATA3. Of the evaluable cases, 167 were designated as luminal (CK5/6- and GATA3+) and 29 as basal (CK5/6+ and GATA3-). Additional sequential TMA sections were stained for CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) (SP263). Basal-subtype tumours showed a trend towards worse disease-specific survival (P = 0.078). There were statistically significant associations between basal subtype and CD8 expression (P = 0.008), PD-1 expression (P = 0.001), and PD-L1 expression (P = 0.014). Lower CD4/CD8 and increased CD8/FOXP3 ratios (P = 0.047 and P = 0.031, respectively) were also identified in the basal-subtype group. CONCLUSIONS: Basal-subtype high-grade UC has an abundance of CD8+ T cells with increased expression of inhibitory markers, indicative of a 'hot' immunophenotype.
Authors: Sandra van Wilpe; Mark A J Gorris; Lieke L van der Woude; Shabaz Sultan; Rutger H T Koornstra; Antoine G van der Heijden; Winald R Gerritsen; Michiel Simons; I Jolanda M de Vries; Niven Mehra Journal: Front Immunol Date: 2022-01-03 Impact factor: 7.561