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Analysis of T cell receptor αβ variability in lymphocytes infiltrating melanoma primary tumours and metastatic lesions

  • Original Articles
  • Malignant Melanoma, Metastasis, Tumourinfiltrating Lymphocytes, T Cell Receptor Variablegene Repertoire, Polymerase Chain Reaction
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Abstract

The T cell receptor (TCR) αβ variable(V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reversetranscription-coupled polymerase chain reaction (RT-PCR). All patients were typed for HLA-A1 and-A2, either serologically or by a newly developed RT-PCR method. Two of these patients expressed HLA-A2, one the HLA-A1 haplotype and one further patient was heterozygous HLA-A1/-A2. The prognostic parameters for all four patients indicated that rapid progression of the disease was to be expected. However, only two of the patients showed rapid progression, while the remaining two patients are still alive after more than 3 years. In TIL in primary melanomas, a possible correlation was suggested between HLA-A2 and the preferential usage of the TCR V gene families Vα4, Vα5, Vα22 and Vβ8, whereas the Vβ3 gene family appeared to be expressed together with HLA-A1. Other highly expressed V gene families, apparently not restricted to either HLA-A1 or-A2, were Vα1 (expressed in three of four primary tumours) and Vα21 (expressed in two of four tumours). We found no evidence suggesting any correlations between the haplotypes HLA-A1 and-A2 and preferential V gene family expression in the metastatic lesions, and the only common feature was Vα8, which was found to be highly expressed in two out of three subcutaneous metastases. The V gene families, which were highly expressed in the primary tumour were generally not, or only very weakly, expressed in metastases and vice versa, possibly reflecting a change in the phenotype of the metastatic melanoma target cells. With regards to patient 0368, it was possible to obtain and study material from two subcutaneous metastases. The first metastasis was excised more than a year after the primary tumour, showing a completely different V region repertoire. The second metastasis was excised at surgery 2 years after primary surgery and likewise showed a dramatic shift in comparison to the first subcutaneous metastasis. Although the present study only included a small number of patients, it suggests that the estimation of V gene expression, if applied to a larger amount of patient material, might make it possible to substantiate further the suggested correlations between the T cell response against the tumour, HLA and antigen expression. Such studies will be of obvious interest in the further analysis of new immunotherapeutic regimens involving the T cell response against tumours.

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Authors and Affiliations

  1. Department of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, DK-2100, Copenhagen, Denmark

    Jørgen Schøller, Per thor Straten, Anette Birck & Jesper Zeuthen

  2. Department of Plastic and Reconstructive Surgery, State University Hospital, DK-2100, Copenhagen, Denmark

    Elsebeth Siim, Karin Dahlström & Krzysztof T. Drzewiecki

Authors
  1. Jørgen Schøller
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  2. Per thor Straten
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  3. Anette Birck
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  4. Elsebeth Siim
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  5. Karin Dahlström
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  6. Krzysztof T. Drzewiecki
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  7. Jesper Zeuthen
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Additional information

This investigation was supported by project grants 92-7580, 92-8525 and 93-7610 from The Danish Cancer Society (J.Z.), and grants from The Novo Foundation (J.S.), The P. Carl Petersen Foundation (J.S.), The Astrid Thaysen Foundation (J.S.) and The Danish Foundation for the Advancement of Medical Science (J.S.). J.S. was the recipient of a Seniot Fellowship from the Danish Cancer Society

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Schøller, J., Straten, P.t., Birck, A. et al. Analysis of T cell receptor αβ variability in lymphocytes infiltrating melanoma primary tumours and metastatic lesions. Cancer Immunol Immunother 39, 239–248 (1994). https://doi.org/10.1007/BF01525987

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  • DOI: https://doi.org/10.1007/BF01525987

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