Waight Jeremy D, Takai Shinji, Marelli Bo, Qin Guozhong, Hance Kenneth W, Zhang Dong, Tighe Robert, Lan Yan, Lo Kin-Ming, Sabzevari Helen, Hofmeister Robert, Wilson Nicholas S
Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
Oncology Section, Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka 541-8564, Japan;
J Immunol. 2015 Feb 1;194(3):878-82. doi: 10.4049/jimmunol.1402725. Epub 2014 Dec 29.
CD4(+) regulatory T cells (Tregs) are critical for maintaining self-tolerance and function to prevent autoimmune disease. High densities of intratumoral Tregs are generally associated with poor patient prognosis, a correlation attributed to their broad immune-suppressive features. Two major populations of Tregs have been defined, thymically derived natural Tregs (nTregs) and peripherally induced Tregs (iTregs). However, the relative contribution of nTregs versus iTregs to the intratumoral Treg compartment remains controversial. Demarcating the proportion of nTregs versus iTregs has important implications in the design of therapeutic strategies to overcome their antagonistic effects on antitumor immune responses. We used epigenetic, phenotypic, and functional parameters to evaluate the composition of nTregs versus iTregs isolated from mouse tumor models and primary human tumors. Our findings failed to find evidence for extensive intratumoral iTreg induction. Rather, we identified a population of Foxp3-stable nTregs in tumors from mice and humans.
CD4(+)调节性T细胞（Tregs）对于维持自身耐受性和预防自身免疫性疾病的功能至关重要。肿瘤内Tregs的高密度通常与患者预后不良相关，这种相关性归因于它们广泛的免疫抑制特性。已定义了两类主要的Tregs，即胸腺来源的天然Tregs（nTregs）和外周诱导的Tregs（iTregs）。然而，nTregs与iTregs对肿瘤内Treg区室的相对贡献仍存在争议。区分nTregs与iTregs的比例对于设计治疗策略以克服它们对抗肿瘤免疫反应的拮抗作用具有重要意义。我们使用表观遗传学、表型和功能参数来评估从小鼠肿瘤模型和原发性人类肿瘤中分离出的nTregs与iTregs的组成。我们的研究结果未能找到肿瘤内广泛诱导iTreg的证据。相反，我们在小鼠和人类的肿瘤中鉴定出了一群Foxp3稳定的nTregs。
