Class I and Class II HLA Antigen Expression by Transitional Cell Carcinoma of the Bladder: Correlation with T-Cell Infiltration and BCG Treatment

Abstract

HLA class I and II glycoproteins from transitional cell carcinoma (TCC) and from perineoplastic and healthy vesical mucosa were characterized together with infiltrating cells by means of immunochemistry using specific monoclonal antibodies on frozen sections obtained during resection or radical cystectomy. Specimens were taken from 11 patients with TCC and five with healthy bladder mucosa. Four patients with TCC and four with healthy mucosa had been previously treated with a course of intravesical bacillus Calmette-Guerin (BCG). Ten out of 11 TCC samples expressed class I glycoproteins with a membrane pattern (diffuse in seven, focal in three) as normal epithelial cells from either controls or perineoplastic bladder. Interestingly, eight out of 11 TCC samples expressed class II antigens on their membrane that were also present in six cases in the perineoplastic tissue while the epithelial cells from four out of five normal bladders were completely negative. The epithelial display of class II antigens in the non-neoplastic areas and in the normal bladder correlates (p less than 0.001) with the degree of cellular infiltrate while such a relationship was not found between the HLA II expression of neoplastic cells and the infiltrate. BCG treatment was associated with a higher amount of inflammatory cells, prevalently T "activated" cells (CD5+,DR+), with a CD4/CD8 ratio always greater than 1. In the light of the role played by HLA glycoproteins in immune mechanisms, these results could help explain the positive action of BCG and the relative immunosensitivity of TCC.

Expression of Markers for Transitional Cell Carcinoma in Normal Bladder Mucosa of Patients with Bladder Cancer

“…22 Only scant data on the relation between HLA-II ex pression and bladder cancer have been published and al though HLA-II expression was found in bladder cancer and correlated with B C G therapy23,24 and was induced by cyto kines,25 no correlation has been found between HLA-II ex pression and tumor aggressiveness. 24,26 A consistent value of the epidermal growth factor receptor (EGF-R) in T C C has been recently reported.9-27 Normally, EGF-R is found only on the basal layer of epithelial cells. In bladder tumors the urinary concentration of E G F can be decreased, but EGF-R expression in tumors is higher than in normal urothelium.…”

Surface antigen expression on bladder tumor cells induced by bacillus Calmette‐Guérin (BCG): A role of BCG internalization into tumor cells

“…MHC Class II antigens serve as restriction elements for cells that present antigens to CD4 + helper T cells, and it has been reported that intravesical BCG treatment induces the expression of MHC Class II on normal urothelium and bladder tumor cells in patients. [8][9][10][11][12] The CD1 family are class I-like antigen presentation molecules, and it is reported that glycolipids of mycobacteria, including BCG, serve as their ligands and activate NKT cells and may have an important role in the antitumor effect. 13 Considered most important for T cell activation as a major ligand of CD28 is CD80 (B7-1), which is a major costimulatory molecule.…”

Immunological protection induced by bacillus Calmette–Guérin treatment in a murine bladder tumor model

“…Chronic bladder‐wall infiltration of immune cells, such as T lymphocytes (predominantly CD4 + T cells) and activated macrophages has been reported 6 . BCG is also known to induce MHC class II molecules 7 and intracellular adhesion molecule (ICAM)‐1 molecule expression 8 in normal and tumor urothelial cells. In an animal model, Ratliff et al 9 .…”