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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Accumulation of identical T cells in melanoma and vitiligo-like leukoderma
J C Becker1, P Guldberg, J Zeuthen
1Department of Dermatology, Julius-Maximilians-University, Würzburg, Germany. becker-jc.derma@mail.uni-wuerzburg.de
Abstract:
The cloning of genes encoding melanoma antigens has opened new possibilities for the treatment of patients with cancer; however, most tumor rejection antigens recognized by tumor infiltrating lymphocytes are the products of genes that are also expressed by normal melanocytes. Hence, a large set of antigenic determinants of the self have not induced self-tolerance and these peptide determinants furnish target structures for immune responses directed against tumors. The notion that the immunotherapeutic targets involved in cancer regression comprise normal differentiation antigens is stressed by the association between vitiligo-like leukoderma, due to destruction of normal melanocytes, and melanoma regression, due to destruction of cancer cells. Nevertheless, this is the first report to demonstrate by means of a new technique based on reverse transcription polymerase chain reaction and denaturing gradient gel electrophoresis, the presence of clonally expanded T cells with identical BV regions in areas of destruction of both normal and neoplastic cells.
Insights
Cancer immunotherapies target normal self-antigens found on melanoma cells. This study found identical T-cells attacking both cancerous and normal melanocytes, suggesting a shared immune response pathway.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cloning melanoma antigens offers cancer treatment potential.
- Many tumor rejection antigens are also expressed by normal melanocytes.
- Self-antigens on cancer cells can trigger immune responses due to lack of self-tolerance.
Purpose of the Study:
- To investigate the immune response against shared antigens in melanoma.
- To demonstrate the presence of clonally expanded T-cells in both tumor and normal melanocyte destruction sites.
Main Methods:
- Utilized a novel technique combining reverse transcription polymerase chain reaction (RT-PCR) and denaturing gradient gel electrophoresis (DGGE).
- Analyzed T-cell receptor beta variable (BV) regions to identify clonal expansion.
Main Results:
- Identified clonally expanded T-cells with identical BV regions.
- Demonstrated the presence of these T-cells in areas of both normal melanocyte and neoplastic cell destruction.
- This indicates a shared immune response targeting both normal and cancerous cells.
Conclusions:
- Normal differentiation antigens are key targets in cancer immunotherapy.
- The immune system can mount responses against self-antigens expressed by tumors.
- Vitiligo-like leukoderma and melanoma regression share a common immunological basis involving T-cell responses.
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