CD4+ T cell responses to SSX-4 in melanoma patients.
Genes of the synovial sarcoma X breakpoint (SSX) family are expressed in different human tumors, including melanomas, but not in adult somatic tissues. Because of their specific expression at the tumor site, SSX-encoded Ags are potential targets for anticancer immunotherapy. In this study, we have analyzed CD4+ T cell responses directed against the Ag encoded by SSX-4. Upon in vitro stimulation of PBMC from four melanoma patients bearing Ag-expressing tumors with a pool of long peptides spanning the protein sequence, we detected and isolated SSX-4-specific CD4+ T cells recognizing several distinct antigenic sequences, mostly restricted by frequently expressed HLA class II alleles. The majority of the identified sequences were located within the Krüppel-associated box domain in the N-terminal region of the protein, indicating a high potential immunogenicity of this region. Together our data document the existence of CD4+ T cells specific for multiple SSX-4 derived sequences in circulating lymphocytes from melanoma patients and encourage further studies to assess the impact of SSX-4-specific T cell responses on disease evolution in cancer patients.
Ayyoub
Maha
M
Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Merlo
Andrea
A
Hesdorffer
Charles S
CS
Rimoldi
Donata
D
Speiser
Daniel
D
Cerottini
Jean-Charles
JC
Chen
Yao-Tseng
YT
Old
Lloyd J
LJ
Stevanovic
Stefan
S
Valmori
Danila
D
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins