Publication: Investigation of tnfr2 regulatory t cells and associated cytokines on the pathogenesis of nasopharyngeal carcinoma
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Date
2023-09
Authors
Rahman, Engku Nur Syafirah Engku Abd
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Abstract
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.