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Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2

CD1d-restricted Vα24-Jα18–invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs us...

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Autores principales: Metelitsa, Leonid S., Wu, Hong-Wei, Wang, Hong, Yang, Yujun, Warsi, Zamir, Asgharzadeh, Shahab, Groshen, Susan, Wilson, S. Brian, Seeger, Robert C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211904/
https://www.ncbi.nlm.nih.gov/pubmed/15123743
http://dx.doi.org/10.1084/jem.20031462
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author Metelitsa, Leonid S.
Wu, Hong-Wei
Wang, Hong
Yang, Yujun
Warsi, Zamir
Asgharzadeh, Shahab
Groshen, Susan
Wilson, S. Brian
Seeger, Robert C.
author_facet Metelitsa, Leonid S.
Wu, Hong-Wei
Wang, Hong
Yang, Yujun
Warsi, Zamir
Asgharzadeh, Shahab
Groshen, Susan
Wilson, S. Brian
Seeger, Robert C.
author_sort Metelitsa, Leonid S.
collection PubMed
description CD1d-restricted Vα24-Jα18–invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs using TaqMan(®) reverse transcription polymerase chain reaction and immunofluorescent microscopy. 52 tumors (53%) contained iNKTs, and oligonucleotide microarray analysis of the iNKT(+) and iNKT(−) tumors revealed that the former expressed higher levels of CCL2/MCP-1, CXCL12/SDF-1, CCL5/RANTES, and CCL21/SLC. Eight tested neuroblastoma cell lines secreted a range of CCL2 (0–21.6 ng/ml), little CXCL12 (≤0.1 ng/ml), and no detectable CCL5 or CCL21. CCR2, the receptor for CCL2, was more frequently expressed by iNKT compared with natural killer and T cells from blood (P < 0.001). Supernatants of neuroblastoma cell lines that produced CCL2 induced in vitro migration of iNKTs from blood of patients and normal adults; this was abrogated by an anti-CCL2 monoclonal antibody. CCL2 expression by tumors was found to inversely correlate with MYCN proto-oncogene amplification and expression (r = 0.5, P < 0.001), and MYCN-high/CCL2-low expression accurately predicted the absence of iNKTs (P < 0.001). In summary, iNKTs migrate toward neuroblastoma cells in a CCL2-dependent manner, preferentially infiltrating MYCN nonamplified tumors that express CCL2.
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spelling pubmed-22119042008-03-11 Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2 Metelitsa, Leonid S. Wu, Hong-Wei Wang, Hong Yang, Yujun Warsi, Zamir Asgharzadeh, Shahab Groshen, Susan Wilson, S. Brian Seeger, Robert C. J Exp Med Article CD1d-restricted Vα24-Jα18–invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs using TaqMan(®) reverse transcription polymerase chain reaction and immunofluorescent microscopy. 52 tumors (53%) contained iNKTs, and oligonucleotide microarray analysis of the iNKT(+) and iNKT(−) tumors revealed that the former expressed higher levels of CCL2/MCP-1, CXCL12/SDF-1, CCL5/RANTES, and CCL21/SLC. Eight tested neuroblastoma cell lines secreted a range of CCL2 (0–21.6 ng/ml), little CXCL12 (≤0.1 ng/ml), and no detectable CCL5 or CCL21. CCR2, the receptor for CCL2, was more frequently expressed by iNKT compared with natural killer and T cells from blood (P < 0.001). Supernatants of neuroblastoma cell lines that produced CCL2 induced in vitro migration of iNKTs from blood of patients and normal adults; this was abrogated by an anti-CCL2 monoclonal antibody. CCL2 expression by tumors was found to inversely correlate with MYCN proto-oncogene amplification and expression (r = 0.5, P < 0.001), and MYCN-high/CCL2-low expression accurately predicted the absence of iNKTs (P < 0.001). In summary, iNKTs migrate toward neuroblastoma cells in a CCL2-dependent manner, preferentially infiltrating MYCN nonamplified tumors that express CCL2. The Rockefeller University Press 2004-05-03 /pmc/articles/PMC2211904/ /pubmed/15123743 http://dx.doi.org/10.1084/jem.20031462 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Metelitsa, Leonid S.
Wu, Hong-Wei
Wang, Hong
Yang, Yujun
Warsi, Zamir
Asgharzadeh, Shahab
Groshen, Susan
Wilson, S. Brian
Seeger, Robert C.
Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title_full Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title_fullStr Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title_full_unstemmed Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title_short Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2
title_sort natural killer t cells infiltrate neuroblastomas expressing the chemokine ccl2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211904/
https://www.ncbi.nlm.nih.gov/pubmed/15123743
http://dx.doi.org/10.1084/jem.20031462
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