PMID- 17545540
OWN - NLM
STAT- MEDLINE
DCOM- 20070817
LR  - 20201222
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 11
DP  - 2007 Jun 1
TI  - Functional up-regulation of human leukocyte antigen class I antigens expression 
      by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications.
PG  - 3333-8
AB  - PURPOSE: To investigate the potential of the DNA hypomethylating agent 
      5-aza-2'-deoxycytidine (5-aza-CdR) to improve the effectiveness of 
      immunotherapeutic approaches against melanocyte differentiation antigens. 
      EXPERIMENTAL DESIGN: The effect of 5-aza-CdR on the constitutive expression of 
      gp100 was investigated in 11 human melanoma cell lines by real-time reverse 
      transcription-PCR and indirect immunofluorescence (IIF) analyses. 
      5-aza-CdR-mediated changes in the levels of expression of human leukocyte antigen 
      (HLA) class I antigens and HLA-A2 allospecificity, intercellular adhesion 
      molecule-1 (ICAM-1), and leukocyte-function-associated antigen-3 were 
      investigated by IIF analysis on melanoma cells under study. The recognition of 
      gp100-positive Mel 275 melanoma cells, treated or not with 5-aza-CdR, by 
      HLA-A2-restricted gp100((209-217))-specific CTL was investigated by 
      (51)Cr-release assays, IFN-gamma release and IFN-gamma ELISPOT assays. RESULTS: 
      The constitutive expression of gp100 was not affected by 5-aza-CdR on all 
      melanoma cells investigated. Compared with untreated cells, the exposure of Mel 
      275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up-regulated their 
      expression of HLA class I antigens and of ICAM-1. These phenotypic changes 
      significantly (P < 0.05) increased the lysis of 5-aza-CdR-treated Mel 275 
      melanoma cells by gp100-specific CTL and increased their IFN-gamma release. 
      5-aza-CdR treatment of Mel 275 cells also induced a higher number of 
      gp100-specific CTL to secrete IFN-gamma. CONCLUSIONS: Treatment with 5-aza-CdR 
      improves the recognition of melanoma cells by gp100-specific CTL through the 
      up-regulation of HLA class I antigens expression; ICAM-1 also contributes to this 
      phenomenon. These findings highlight a broader range of therapeutic implications 
      of 5-aza-CdR when used in association with active or adoptive immunotherapeutic 
      approaches against a variety of melanoma-associated antigens.
FAU - Fonsatti, Ester
AU  - Fonsatti E
AD  - Division of Medical Oncology and Immunotherapy, Department of Oncology, 
      University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
FAU - Nicolay, Hugues J M
AU  - Nicolay HJ
FAU - Sigalotti, Luca
AU  - Sigalotti L
FAU - Calabro, Luana
AU  - Calabro L
FAU - Pezzani, Laura
AU  - Pezzani L
FAU - Colizzi, Francesca
AU  - Colizzi F
FAU - Altomonte, Maresa
AU  - Altomonte M
FAU - Guidoboni, Massimo
AU  - Guidoboni M
FAU - Marincola, Francesco M
AU  - Marincola FM
FAU - Maio, Michele
AU  - Maio M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 776B62CQ27 (Decitabine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Azacitidine/*analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - Decitabine
MH  - Fluorescent Antibody Technique, Indirect
MH  - *Gene Expression Regulation, Neoplastic
MH  - Histocompatibility Antigens Class I/*biosynthesis
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Interferon-gamma/metabolism
MH  - Melanoma/*drug therapy/*immunology
MH  - Membrane Glycoproteins/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin Neoplasms/*drug therapy/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology/metabolism
MH  - Up-Regulation
MH  - gp100 Melanoma Antigen
EDAT- 2007/06/05 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/06/05 09:00
PHST- 2007/06/05 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/06/05 09:00 [entrez]
AID - 13/11/3333 [pii]
AID - 10.1158/1078-0432.CCR-06-3091 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Jun 1;13(11):3333-8. doi: 10.1158/1078-0432.CCR-06-3091.