Treg为肿瘤免疫逃逸领域热点问题。我们前期证实肿瘤微环境M2型巨噬细胞（Mø-2）通过促进Treg分化增强头颈鳞癌免疫逃逸，但Mø-2促进Treg分化的机制不清。我们最新研究证实IL-33可诱导Treg分化，预实验结果显示氧化应激状态下Mø-2中Nrf2失活，活化Nrf2可降低Mø-2胞浆中IL-33表达。推测：肿瘤微环境氧化应激通过调控Mø-2中Nrf2失活促进IL-33分泌，后者通过调控Treg分化促进头颈鳞癌免疫逃逸。本研究拟探讨肿瘤微环境氧化应激调控Mø-2中Nrf2失活促进IL-33分泌的分子机制及Mø-2氧化应激状态变化；探讨活化Mø-2中Nrf2对拮抗IL-33介导的Treg分化的有效性；动物实验探讨Nrf2缺失与活化状态下肿瘤微环境Mø-2对IL-33胞外转运和Treg分化的调控。该研究有望从肿瘤代谢氧化应激为切入点，为以Mø-2中Nrf2为靶点的头颈鳞癌免疫治疗提供依据

Treg is a hot issue in the field of tumor immune escape. We previously confirmed that M2 macrophages (Mø-2) in tumor microenvironment enhanced immune escape of head and neck squamous cell carcinoma (HNSCC) via promoting Treg differentiation. However, the mechanism of Treg differentiation promoted by Mø-2 is unclear. Our latest study revealed that IL-33 could induce Treg differentiation. Pre-experimental results showed that Nrf2 in Mø-2 was inactivated under oxidative stress, and activation of Nrf2 could reduce the expression of IL-33 in the cytoplasm of Mø-2. We speculated that oxidative stress in tumor microenvironment could promote the secretion of IL-33 by regulating the inactivation of Nrf2 in Mø-2, then IL-33 promotes the immune escape of HNSCC by regulating Treg differentiation. The purpose of this study was to investigate the molecular mechanism of IL-33 secretion promoted by Nrf2 inactivation in Mø-2 and the changes of Mø-2 oxidative stress state, and to investigated the effectiveness of Nrf2 activation in antagonizing IL-33-mediated Treg differentiation. Moreover, in vivo study will be carried out to investigated IL-23 extracellular transport and Treg differentiation regulated by tumor microenvironment Mø-2 under the condition of Nrf2 deletion and activation, respectively. This study, with the perspective of oxidative stress of tumor metabolism, is expected to provide evidence for HNSCC immunotherapy of targeting Nrf2 in Mø-2.