Bacillus Calmette-Guerin immunotherapy of bladder cancer induces selection of human leukocyte antigen class I-deficient tumor cells Carretero Coca, Rafael Cabrera Castillo, María Teresa Gil, Hernani Sáenz-López, Pablo Maleno, Isabel Aptsiauri, Natalia Cózar Olmo, José Manuel Garrido Torres-Puchol, Federico Cancer Immunotherapy BCG Bladder HLA Department of Clinical Analysis, Virgen de las Nieves University Hospital, Granada Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Spain Department of Urology, Virgen de las Nieves University Hospital, Granada 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. 2025-11-04T09:16:46Z 2025-11-04T09:16:46Z 2011-08-15 journal article Carretero Coca, Rafael. Int J Cancer. 2011 Aug 15;129(4):839-46. doi: 10.1002/ijc.25733. Epub 2011 Jun 10. https://doi.org/10.1002/ijc.25733 https://hdl.handle.net/10481/107728 10.1002/ijc.25733 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Wiley