Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients.
The pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes...
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2009
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my.upm.eprints.177152012-08-17T01:26:39Z http://psasir.upm.edu.my/id/eprint/17715/ Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. Seow, Heng Fong Abdullah, Maizaton Atmadini Yip, Wai Kien Yusoff, S. M. The pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a double-enzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 non-malignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3ζ and CD3ε was also determined. The prevalence of CD4+FoxP3+ cells in CD4+ T cells and the ratio of FoxP3+/CD8+ were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3+/CD25+FoxP3− in NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25+FoxP3− cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3+/CD25+FoxP3− was found in non-keratinizing and undifferentiated carcinomas. Increased CD4+FoxP3+/CD4+ proportion and FoxP3+/CD8+ ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3ζ in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC. Wiley-Blackwell 2009-03 Article PeerReviewed Seow, Heng Fong and Abdullah, Maizaton Atmadini and Yip, Wai Kien and Yusoff, S. M. (2009) Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. Clinical & Experimental Immunology, 155 (3). pp. 412-422. ISSN 0009-9104 & Online ISSN: 1365-2249 http://onlinelibrary.wiley.com/ 10.1111/j.1365-2249.2008.03793.x. English |
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The pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a double-enzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 non-malignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3ζ and CD3ε was also determined. The prevalence of CD4+FoxP3+ cells in CD4+ T cells and the ratio of FoxP3+/CD8+ were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3+/CD25+FoxP3− in NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25+FoxP3− cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3+/CD25+FoxP3− was found in non-keratinizing and undifferentiated carcinomas. Increased CD4+FoxP3+/CD4+ proportion and FoxP3+/CD8+ ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3ζ in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.
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format |
Article |
author |
Seow, Heng Fong Abdullah, Maizaton Atmadini Yip, Wai Kien Yusoff, S. M. |
spellingShingle |
Seow, Heng Fong Abdullah, Maizaton Atmadini Yip, Wai Kien Yusoff, S. M. Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
author_facet |
Seow, Heng Fong Abdullah, Maizaton Atmadini Yip, Wai Kien Yusoff, S. M. |
author_sort |
Seow, Heng Fong |
title |
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
title_short |
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
title_full |
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
title_fullStr |
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
title_full_unstemmed |
Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
title_sort |
increase in tumour-infiltrating lymphocytes with regulatory t cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. |
publisher |
Wiley-Blackwell |
publishDate |
2009 |
url |
http://psasir.upm.edu.my/id/eprint/17715/ http://onlinelibrary.wiley.com/ |
_version_ |
1643826602992205824 |
score |
13.160551 |