Premium
Coordinated downregulation of the antigen presentation machinery and HLA class I/β2‐microglobulin complex is responsible for HLA‐ABC loss in bladder cancer
Author(s) -
Romero Jose María,
Jiménez Pilar,
Cabrera Teresa,
Cózar José Manuel,
Pedrinaci Susana,
Tallada Miguel,
Garrido Federico,
RuizCabello Francisco
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20499
Subject(s) - beta 2 microglobulin , downregulation and upregulation , human leukocyte antigen , mhc class i , antigen processing , major histocompatibility complex , cancer research , immunology , biology , antigen presentation , bladder cancer , immune system , cancer , antigen , t cell , gene , genetics
Abstract Downregulation of MHC class I expression is a widespread phenomenon used by tumor cells to escape antitumor T‐cell‐mediated immune responses. These alterations may play a role in the clinical course of the disease. The aim of our study was to investigate the molecular mechanism underlying the absence of HLA‐class I molecule expression in bladder cancer cells. Microdissected tumor tissues were characterized by real‐time quantitative PCR for the expression of HLA‐ABC, β2‐microglobulin and the members of the antigen processing machinery (APM) of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). Our results showed that irreversible HLA loss by mutations in the β2‐microglobulin gene was not the cause of low HLA class I expression in bladder cancers. In contrast, we observed a coordinated transcription downregulation of HLA‐ABC and β2‐microglobulin and APM genes in microdissected tumor tissue derived from bladder carcinomas. This mechanism may represent a major factor for the downregulation of HLA class I expression and in the subsequent direct recognition of cancer cells by cytolytic T lymphocytes. Because this regulatory mechanism is frequently reversible by IFN‐gamma treatment, we conclude that HLA class I expression should be a major consideration for immunotherapeutic purposes in patients with bladder cancer.