Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma.


METHODS
Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated.


RESULTS
Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors.


CONCLUSIONS
This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.
Korangy
Firouzeh
F
Department of Gastroenterology, Hepatology and Endocrinology, Clinic of Visceral and Transplantation Surgery, Medizinische Hochschule Hannover, Hannover, Germany.
Ormandy
Lars A
LA
Bleck
Jörg S
JS
Klempnauer
Jürgen
J
Wilkens
Ludwig
L
Manns
Michael P
MP
Greten
Tim F
TF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002860:Chromium Radioisotopes / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007167:Immunotherapy / Q000379:methods*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000906:Antibodies; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D002860:Chromium Radioisotopes; D018984:Epitopes, T-Lymphocyte; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins