Tumor Infiltrating Lymphocytes in Melanoma Comprise High Numbers of T-Cell Clonotypes That Are Lost during in Vitro Culture

Melanoma is generally accepted as being an antigenic tumor capable of eliciting T-cell responses that, however, in most cases are inadequate to control tumor growth. Tumor-infiltrating lymphocytes (TIL) in melanoma lesions comprise clonotypic T cells, indicating the in situ recognition of melanoma-a...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2000-08, Vol.96 (2), p.94-99
Main Authors: thor Straten, Per, Kirkin, Alexei F., Siim, Elsebeth, Dahlström, Karin, Drzewiecki, Krzysztof T., Seremet, Tina, Zeuthen, Jesper, Becker, Jürgen C., Guldberg, Per
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Count
Cell Separation
Cells, Cultured
Clone Cells - cytology
Electrophoresis, Polyacrylamide Gel - methods
Flow Cytometry
Host-tumor relations. Immunology. Biological markers
Humans
Lymphocytes, Tumor-Infiltrating - cytology
Medical sciences
Melanoma - pathology
Protein Denaturation
T-Lymphocytes - cytology
Tumors
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Summary:Melanoma is generally accepted as being an antigenic tumor capable of eliciting T-cell responses that, however, in most cases are inadequate to control tumor growth. Tumor-infiltrating lymphocytes (TIL) in melanoma lesions comprise clonotypic T cells, indicating the in situ recognition of melanoma-associated peptide epitopes. Cultured TIL have been studied in order to unveil characteristics of TIL and the interactions of TIL and melanoma cells. Whether in vitro cultured TIL mirrors the in situ situation has, however, been questioned. In the present study we have taken advantage of T-cell receptor clonotype mapping methodology to conduct a full and detailed analysis of the T-cell clonotypes in melanoma lesions and in corresponding lines of TIL established in vitro. All melanoma lesions and the corresponding TIL cultures comprised high numbers of T-cell clonotypes, typically in the range of 40 to more than 60. The subsequent comparison of T-cell clonotypes present in the original lesions and in the corresponding T-cell lines established in vitro demonstrated that a very limited number of the T-cell clonotypes established in vitro are identical to the T-cell clonotypes expanded in situ. These results demonstrate that in situ T-cell clonotypes in melanoma are not readily expanded in vitro and that the majority of T-cell clonotypes present in cultured TIL are not present in situ.
ISSN:1521-6616
1521-7035
DOI:10.1006/clim.2000.4890