Oligoclonality of CD8+ T cells in breast cancer patients.
Substantial evidence has suggested that T cells play an important role in antitumor immunity. T cells with cytotoxic activity against tumors have been isolated from in vitro culture of tumor-infiltrated lymphocytes of cancer patients. In addition, clonal expansions of T cells have been identified in lesions of tumors by using a PCR-based CDR3 analysis of T cell receptors (TCR). Since the CDR3 region of the T cell receptor directly interacts with the antigen-MHC complex and is thus highly polymorphic, a dominant CDR3 length in a particular TCR V beta population will indicate the clonal expansion of a specific T cell clone. Utilizing this technique, we have analyzed the T cell repertoire in lymph nodes (LNs) and peripheral blood of 20 breast cancer patients. Our results show that in most cases, peripheral blood mononuclear cells (PB-MCs) and LN express dominant CD8+ T cell clones in different V beta gene families, and the number of dominant clones is higher in PBMC than in the LN. Furthermore, in 7 out of 16 patients' lymph nodes, there is a dominant V beta 18 T cell clonal expansion in the CD8+ T cell subset. The frequency of an oligoclonal expansion of V beta 18 CD8+ T cells in non-breast cancer lymph nodes is 1 out of 9, but no obvious motif in the CDR3 region of V beta 18 TCR can be identified. The prevalence of the clonal dominance found in breast cancer is discussed in the context of a possible tumor-related antigen stimulation.
Ito
K
K
Department of Medicine, North Shore University Hospital-New York University Medical College, Manhasset, USA.
Fetten
J
J
Khalili
H
H
Hajdu
S
S
Busch
E
E
Pergolizzi
R
R
Vinciguerra
V
V
Chang
M D
MD
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D017931:DNA Primers; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D016376:Oligonucleotides, Antisense; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D016693:Receptors, Antigen, T-Cell, alpha-beta