Aberrant frequency of TNFR2-expressing CD4+ FoxP3+ regulatory T cells in nasopharyngeal carcinoma patients

Abstract

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. The expression levels of selected cytokines were also determined. The results demonstrated that in both peripheral blood (PB) (10.45 ± 5.71%) and tumour microenvironment (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, our research implies that TNFR2 expression by PB and TME Tregs may be a useful predictive indicator in NPC patients.