Departments of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Department of Obstetrics and Gynecology, Center for Gynecological Oncology Amsterdam (CGOA) Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
J Immunother Cancer. 2019 Jan 18;7(1):14. doi: 10.1186/s40425-019-0497-0.
Regulatory T cells (Tregs) may comprise different subsets allowing them to efficiently suppress different types of effector T cells. In this study, we show that high numbers of both conventional and Tbet co-expressing Foxp3 Tregs accumulate in human papilloma virus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC). The infiltration of Tbet+ Foxp3+ Tregs was strongly correlated with a concomitant tumor-specific and conventional type 1-oriented intratumoral T cell infiltrate. Both conventional CD4+CD25+CD127-Foxp3 Tregs and their Tbet counterparts exhibited an activated phenotype, co-expressed high levels of CTLA4 and Helios and exhibited a maximally demethylated Foxp3 gene locus TSDR, indicating their full capacity to impede a type 1 effector T cell response. Interestingly, while the prognostic value of conventional Tregs was neutral, a high intratumoral frequency of Tbet+ Tregs was associated with prolonged disease-specific survival, most likely because their presence reflected high numbers of effector T cells. The presence of these Tbet+ Tregs may in part explain why a dense type 1-oriented immune infiltrate in OPSCC is not enough to fully control tumor growth.
调节性 T 细胞（Tregs）可能包含不同的亚群，使它们能够有效地抑制不同类型的效应 T 细胞。在这项研究中，我们表明，在人乳头瘤病毒（HPV）驱动的口咽鳞状细胞癌（OPSCC）中，大量的传统 Treg 和 Tbet 共表达 Foxp3 Treg 会累积。Tbet+Foxp3+Treg 的浸润与肿瘤特异性和传统的 1 型偏向的肿瘤内 T 细胞浸润密切相关。传统的 CD4+CD25+CD127-Foxp3 Treg 及其 Tbet 对应物均表现出激活表型，共表达高水平的 CTLA4 和 Helios，并表现出最大程度去甲基化的 Foxp3 基因座 TSDR，表明它们完全有能力抑制 1 型效应 T 细胞反应。有趣的是，虽然传统 Treg 的预后价值是中性的，但肿瘤内 Tbet+Treg 的高频率与延长的疾病特异性生存相关，这很可能是因为它们的存在反映了大量的效应 T 细胞。这些 Tbet+Treg 的存在可能部分解释了为什么 OPSCC 中密集的 1 型偏向免疫浸润不足以完全控制肿瘤生长。
