Blood T-cell Vbeta transcriptome in melanoma patients.
Tumor-cells have been shown to elicit MHC-restricted and antigen-specific T-cell responses. In this article, we used a new approach to study T-cell responses in tumor-bearing patients based on a global representation of the Vbeta-transcriptome, making it possible to grade CDR3-length distribution (CDR3-LD) alterations. Six patients with advanced melanoma disease, from whom blood samples were taken before and serially after tyrosinase-A peptide vaccination, were studied. The PBMC from patients displayed highly significant Vbeta transcriptome alterations as compared to healthy individuals. Similar Vbeta alterations could be detected both in PBMCs and at the tumor site. After vaccination, Vbeta alterations could also be observed by gauging individually their transcript level but not their cell-surface expression. Some Vbeta families exhibited high Vbeta/HPRT transcript ratios (e.g., Vbeta1), which represented up to 44% of the whole transcriptome, a situation that was not reflected by an increase in the percentage of T cells that expressed the corresponding protein and was not observed in normal individuals. In several instances, CDR3-LD altered T cells exhibited MHC-restricted and tumor-specific IFNgamma or GM-CSF production. Finally, we show that the presence of a tumor and probably vaccination can affect Vbeta transcriptome patterns and induce specific clones reactive to autologous tumor or vaccinating peptides. In combination with other methods, such an approach should help in identifying the clones actually involved in the response against the tumor.
Degauque
Nicolas
N
Institut National de la Santé et de la Recherche Médicale-Unité 437: Immunointervention dans les Allo et Xénotransplantations and Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Schadendorf
Dirk
D
Brouard
Sophie
S
Guillet
Marina
M
Sébille
Fabien
F
Höhn
Hanni
H
Pallier
Annaïck
A
Ruiz
Catherine
C
Dupont
Alexandre
A
Chapin
Stéphane
S
Hofmann
Udo
U
Maeurer
Markus
M
Soulillou
Jean-Paul
JP
D000328:Adult; D000368:Aged; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008545:Melanoma / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D010455:Peptides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014442:Monophenol Monooxygenase