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Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma

Tumour necrosis factor receptor type 2 (TNFR2) is a surface marker of highly suppressive subset of CD4+FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migrat...

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Main Author: Rahman, Engku Nur Syafirah Engku Abd
Format: Thesis
Language:English
Published: 2023
Subjects:
R Medicine
RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
Online Access:http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf
http://eprints.usm.my/59813/
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spelling my.usm.eprints.59813 http://eprints.usm.my/59813/ Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma Rahman, Engku Nur Syafirah Engku Abd R Medicine RC254-282 Neoplasms. Tumors. Oncology (including Cancer) Tumour necrosis factor receptor type 2 (TNFR2) is a surface marker of highly suppressive subset of CD4+FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migration, survival of TNFR2+ Tregs, and association with clinicopathological characteristics were assessed in the peripheral blood (PB) (n = 29) and tumour microenvironment (TME) (n = 7) of NPC patients in comparison with healthy controls (n = 29). The expression levels of selected cytokines were also determined. Samples were evaluated for Tregs (CD4+FoxP3+, CD4+FoxP3+TNFR2+, and CD4+CD25+CD127low/-FoxP3+TNFR2+) using multicolor flow cytometry. The results demonstrated that in both PB (10.45 ± 5.71%) and TME (54.38 ± 16.15%) of NPC patients, Tregs expressed TNFR2 at noticeably greater levels than conventional T cells (Tconvs) (3.91 ± 2.62%, p < 0.0001), akin to healthy controls. Expression of TNFR2 (1.06 ± 0.99%) was correlated better than CD25+ (0.40 ± 0.46%) and CD127-/low (1.00 ± 0.83%) with FoxP3 expression in NPC PB (p = 0.0005). Though there was no significant association between TNFR2 expression with the functional capacity (proliferation, migration and survival) of Tregs (p > 0.05), the proportions of PB and TME TNFR2+ Tregs in NPC patients showed more proliferative, higher migration capacity, and better survival ability, as compared to those in healthy controls. Furthermore, TNFR2+ Tregs from NPC patients expressed significantly higher amounts of IL-6 (p = 0.0077), IL-10 (p = 0.0001), IFN-γ (p = 0.0105), and TNF-α (p < 0.0001) than those from healthy controls. Most significantly, TNFR2 expression in maximally suppressive Tregs population were linked to WHO Type III histological type, distant metastasis, progressive disease status, and poor prognosis for NPC patients. Hence, this research implies that TNFR2 expression by PB and TME Tregs may be a useful predictive indicator in NPC patients. 2023-09 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf Rahman, Engku Nur Syafirah Engku Abd (2023) Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma. PhD thesis, Universiti Sains Malaysia.
institution Universiti Sains Malaysia
building Hamzah Sendut Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Sains Malaysia
content_source USM Institutional Repository
url_provider http://eprints.usm.my/
language English
topic R Medicine
RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
spellingShingle R Medicine
RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
Rahman, Engku Nur Syafirah Engku Abd
Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
description Tumour necrosis factor receptor type 2 (TNFR2) is a surface marker of highly suppressive subset of CD4+FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migration, survival of TNFR2+ Tregs, and association with clinicopathological characteristics were assessed in the peripheral blood (PB) (n = 29) and tumour microenvironment (TME) (n = 7) of NPC patients in comparison with healthy controls (n = 29). The expression levels of selected cytokines were also determined. Samples were evaluated for Tregs (CD4+FoxP3+, CD4+FoxP3+TNFR2+, and CD4+CD25+CD127low/-FoxP3+TNFR2+) using multicolor flow cytometry. The results demonstrated that in both PB (10.45 ± 5.71%) and TME (54.38 ± 16.15%) of NPC patients, Tregs expressed TNFR2 at noticeably greater levels than conventional T cells (Tconvs) (3.91 ± 2.62%, p < 0.0001), akin to healthy controls. Expression of TNFR2 (1.06 ± 0.99%) was correlated better than CD25+ (0.40 ± 0.46%) and CD127-/low (1.00 ± 0.83%) with FoxP3 expression in NPC PB (p = 0.0005). Though there was no significant association between TNFR2 expression with the functional capacity (proliferation, migration and survival) of Tregs (p > 0.05), the proportions of PB and TME TNFR2+ Tregs in NPC patients showed more proliferative, higher migration capacity, and better survival ability, as compared to those in healthy controls. Furthermore, TNFR2+ Tregs from NPC patients expressed significantly higher amounts of IL-6 (p = 0.0077), IL-10 (p = 0.0001), IFN-γ (p = 0.0105), and TNF-α (p < 0.0001) than those from healthy controls. Most significantly, TNFR2 expression in maximally suppressive Tregs population were linked to WHO Type III histological type, distant metastasis, progressive disease status, and poor prognosis for NPC patients. Hence, this research implies that TNFR2 expression by PB and TME Tregs may be a useful predictive indicator in NPC patients.
format Thesis
author Rahman, Engku Nur Syafirah Engku Abd
author_facet Rahman, Engku Nur Syafirah Engku Abd
author_sort Rahman, Engku Nur Syafirah Engku Abd
title Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
title_short Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
title_full Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
title_fullStr Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
title_full_unstemmed Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
title_sort investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
publishDate 2023
url http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf
http://eprints.usm.my/59813/
_version_ 1792151166541365248
score 13.211869

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