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
Online Access:	http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf
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spelling	my-usm-ep.598132024-02-13T07:54:21Z Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma 2023-09 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 http://eprints.usm.my/59813/ http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Kesihatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R Medicine R Medicine
spellingShingle	R Medicine R Medicine 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
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
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
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Kesihatan
publishDate	2023
url	http://eprints.usm.my/59813/1/ENGKU%20NUR%20SYAFIRAH%20BT%20ENGKU%20ABD%20RAHMAN-FINAL%20THESIS%20P-UD002319%28R%29-E.pdf
_version_	1794024061057105920

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

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