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Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes
T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indicati...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820815/ https://www.ncbi.nlm.nih.gov/pubmed/24228230 http://dx.doi.org/10.4161/onci.26014 |
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author | Sittig, Simone P Køllgaard, Tania Grønbæk, Kirsten Idorn, Manja Hennenlotter, Jörg Stenzl, Arnulf Gouttefangeas, Cécile thor Straten, Per |
author_facet | Sittig, Simone P Køllgaard, Tania Grønbæk, Kirsten Idorn, Manja Hennenlotter, Jörg Stenzl, Arnulf Gouttefangeas, Cécile thor Straten, Per |
author_sort | Sittig, Simone P |
collection | PubMed |
description | T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were in the range of 1–17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8(+) TILs differed from that of circulating CD8(+) T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8(+) RCC-infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8(+) TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T-cell clonotypes. |
format | Online Article Text |
id | pubmed-3820815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-38208152013-11-13 Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes Sittig, Simone P Køllgaard, Tania Grønbæk, Kirsten Idorn, Manja Hennenlotter, Jörg Stenzl, Arnulf Gouttefangeas, Cécile thor Straten, Per Oncoimmunology Original Research T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were in the range of 1–17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8(+) TILs differed from that of circulating CD8(+) T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8(+) RCC-infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8(+) TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T-cell clonotypes. Landes Bioscience 2013-09-01 2013-09-26 /pmc/articles/PMC3820815/ /pubmed/24228230 http://dx.doi.org/10.4161/onci.26014 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Original Research Sittig, Simone P Køllgaard, Tania Grønbæk, Kirsten Idorn, Manja Hennenlotter, Jörg Stenzl, Arnulf Gouttefangeas, Cécile thor Straten, Per Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title | Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title_full | Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title_fullStr | Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title_full_unstemmed | Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title_short | Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes |
title_sort | clonal expansion of renal cell carcinoma-infiltrating t lymphocytes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820815/ https://www.ncbi.nlm.nih.gov/pubmed/24228230 http://dx.doi.org/10.4161/onci.26014 |
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