Identification of identical TCRs in primary melanoma lesions and tumor free corresponding sentinel lymph nodes.
It is generally believed that priming of efficient T-cell responses takes place in peripheral lymphoid tissues. Although this notion has been rigidly proven for infectious diseases, direct evidence for lymph node priming of in vivo T-cell responses against tumors is still lacking. In the present study, we conducted a full and nonbiased comparison of T-cell clonotypes in melanoma lesions and corresponding sentinel lymph nodes. Whereas most tumor lesions comprised a high number of T-cell clonotypes, only a small number of clonally expanded T cells were detected in the draining lymph nodes. Comparative clonotype mapping demonstrated the presence of identical T-cell clonotypes in the tumors and the respective sentinel lymph nodes, only when tumor cells were present in the latter. However, taking advantage of clonotype specific PCR amplification, TCR sequences representing clonally expanded T cells at the tumor site could be detected in the lymph nodes draining the tumors even in the absence of tumor cells. Evidence for the tumor-specific characteristics of these cells was obtained by in situ staining with peptide/HLA class I complexes demonstrating the presence of MART-1/HLA-A2- and MAGE-3/HLA-A2-reactive T cells at the tumor site, as well as in the draining lymph node. Our data indicate that T-cell responses to melanoma are primed in the sentinel lymph node by cross presentation of tumor antigens by dendritic cells.
Straten
Per thor
Pt
Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, 2100, Copenhagen, Denmark. ps@cancer.dk
Dahl
Christina
C
Schrama
David
D
Pedersen
Lars Østergaard
LØ
Andersen
Mads Hald
MH
Seremet
Tina
T
Bröcker
Eva-B
EB
Guldberg
Per
P
Becker
Jürgen C
JC
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000276:immunology* / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D018807:Polymorphism, Single-Stranded Conformational; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell