PMID- 20957629 OWN - NLM STAT- MEDLINE DCOM- 20110930 LR - 20160303 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 129 IP - 4 DP - 2011 Aug 15 TI - Bacillus Calmette-Guerin immunotherapy of bladder cancer induces selection of human leukocyte antigen class I-deficient tumor cells. PG - 839-46 LID - 10.1002/ijc.25733 [doi] AB - 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. CI - Copyright (c) 2010 UICC. FAU - Carretero, Rafael AU - Carretero R AD - Department of Clinical Analysis, Virgen de las Nieves University Hospital, and Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Spain. FAU - Cabrera, Teresa AU - Cabrera T FAU - Gil, Hernani AU - Gil H FAU - Saenz-Lopez, Pablo AU - Saenz-Lopez P FAU - Maleno, Isabel AU - Maleno I FAU - Aptsiauri, Natalia AU - Aptsiauri N FAU - Cozar, Jose M AU - Cozar JM FAU - Garrido, Federico AU - Garrido F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110610 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibiotics, Antineoplastic) RN - 0 (BCG Vaccine) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (RNA, Messenger) RN - 50SG953SK6 (Mitomycin) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Adult MH - Aged MH - Antibiotics, Antineoplastic/therapeutic use MH - BCG Vaccine/*administration & dosage/immunology MH - Histocompatibility Antigens Class I/genetics/*metabolism MH - Humans MH - Immunoenzyme Techniques MH - *Immunotherapy MH - Loss of Heterozygosity MH - Male MH - Middle Aged MH - Mitomycin/therapeutic use MH - Neoplasm Recurrence, Local/*diagnosis/immunology/metabolism MH - Predictive Value of Tests MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Treatment Outcome MH - Urinary Bladder Neoplasms/*immunology/*therapy EDAT- 2010/10/20 06:00 MHDA- 2011/10/01 06:00 CRDT- 2010/10/20 06:00 PHST- 2010/06/11 00:00 [received] PHST- 2010/09/27 00:00 [accepted] PHST- 2010/10/20 06:00 [entrez] PHST- 2010/10/20 06:00 [pubmed] PHST- 2011/10/01 06:00 [medline] AID - 10.1002/ijc.25733 [doi] PST - ppublish SO - Int J Cancer. 2011 Aug 15;129(4):839-46. doi: 10.1002/ijc.25733. Epub 2011 Jun 10.