Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients

Belinda Palermo, Rita Campanelli, Stefania Mantovani, Erica Lantelme, Ausilia M. Manganoni, Graziella Carella, GianAntonio Da Prada, Gioacchino Robustelli Della Cuna, François Romagne, Laurent Gauthier Antje Necker, Claudia Giachino

Research output: Contribution to journalArticle

Abstract

While tumor-associated antigen (TAA)-specific CD8+ T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A/MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8+/tetramer+ cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/ MART1 and tyrosinase) were contemporarily present. The TAA-specific cells could represent as much as 1/220 T lymphocytes in the circulating CD8+ population. When tetramers were used to monitor the in vitro expansion of TAA-specific CTL precursors upon antigen-specific stimulation, a diverse expansion potential was evidenced in CTL from the different donors and, more strikingly, in CTL specific for the different TAA. Melan-A/MART1-specific CTL clones derived from two patients exhibited a broad range of avidity. Only the highest avidity clones, representing about 50% of the cases analyzed, were tumor specific. By correlating tetramer staining with clone avidity, we found that tetramer fluorescence intensity could represent a good indicator of TCR affinity, but not of overall clone avidity.

Original languageEnglish
Pages (from-to)412-420
Number of pages9
JournalEuropean Journal of Immunology
Volume31
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Cytotoxic T-Lymphocytes
Neoplasm Antigens
MART-1 Antigen
Melanoma
T-Lymphocytes
Clone Cells
Monophenol Monooxygenase
Melanoma-Specific Antigens
HLA-A2 Antigen
Antigens
Population
Flow Cytometry
Fluorescence
Tissue Donors
Lymphocytes
Staining and Labeling
Skin
Neoplasms

Keywords

  • Cytotoxic T lymphocyte
  • HLA tetramer
  • Human
  • Tumor antigen

ASJC Scopus subject areas

  • Immunology

Cite this

Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients. / Palermo, Belinda; Campanelli, Rita; Mantovani, Stefania; Lantelme, Erica; Manganoni, Ausilia M.; Carella, Graziella; Prada, GianAntonio Da; Della Cuna, Gioacchino Robustelli; Romagne, François; Necker, Laurent Gauthier Antje; Giachino, Claudia.

In: European Journal of Immunology, Vol. 31, No. 2, 2001, p. 412-420.

Research output: Contribution to journalArticle

Palermo, Belinda ; Campanelli, Rita ; Mantovani, Stefania ; Lantelme, Erica ; Manganoni, Ausilia M. ; Carella, Graziella ; Prada, GianAntonio Da ; Della Cuna, Gioacchino Robustelli ; Romagne, François ; Necker, Laurent Gauthier Antje ; Giachino, Claudia. / Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients. In: European Journal of Immunology. 2001 ; Vol. 31, No. 2. pp. 412-420.
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AU - Manganoni, Ausilia M.

AU - Carella, Graziella

AU - Prada, GianAntonio Da

AU - Della Cuna, Gioacchino Robustelli

AU - Romagne, François

AU - Necker, Laurent Gauthier Antje

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AB - While tumor-associated antigen (TAA)-specific CD8+ T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A/MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8+/tetramer+ cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/ MART1 and tyrosinase) were contemporarily present. The TAA-specific cells could represent as much as 1/220 T lymphocytes in the circulating CD8+ population. When tetramers were used to monitor the in vitro expansion of TAA-specific CTL precursors upon antigen-specific stimulation, a diverse expansion potential was evidenced in CTL from the different donors and, more strikingly, in CTL specific for the different TAA. Melan-A/MART1-specific CTL clones derived from two patients exhibited a broad range of avidity. Only the highest avidity clones, representing about 50% of the cases analyzed, were tumor specific. By correlating tetramer staining with clone avidity, we found that tetramer fluorescence intensity could represent a good indicator of TCR affinity, but not of overall clone avidity.

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