Bacillus Calmette-Guerin immunotherapy of bladder cancer induces selection of human leukocyte antigen class I-deficient tumor cells
✍ Scribed by Rafael Carretero; Teresa Cabrera; Hernani Gil; Pablo Saenz-Lopez; Isabel Maleno; Natalia Aptsiauri; Jose M. Cozar; Federico Garrido
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- French
- Weight
- 355 KB
- Volume
- 129
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Bacillus Calmette-Guerin (BCG) immunotherapy is a standard treatment for high-risk non-muscle-infiltrating bladder cancer patients. Although the outcomes are good, cancer relapse is observed in around 40% of patients. We present the comparative analysis of human leukocyte antigen (HLA) class I expression in recurrent bladder tumors in patients treated with mitomycin or BCG. HLA class I expression was analyzed by RT-Q-PCR and immunohistochemical techniques. Loss of heterozygosity (LOH) was determined by microsatellite amplification of markers in chromosome 6 and 15. More profound alterations in HLA class I expression were found in post-BCG recurrent tumors than in pre-BCG lesions, whereas mitomycin treatment did not change the HLA class I expression pattern. Post-BCG recurrent tumors also showed a higher incidence of structural defects underlying altered HLA class I expression. We hypothesize that the immunotherapy-activated immune system recognizes and eliminates tumor cells with reversible (''soft'') HLA class I changes but not transformed cells with additional, irreversible (''hard'') alterations. To our knowledge, this is the first clinical evidence of immunotherapy-induced immunoselection of HLA class I loss tumor variants in bladder cancer, although the study involved a small number of patients.