肾透明细胞癌（ccRCC）对传统化放疗均不敏感，故免疫疗法在ccRCC中尤为重要。2018年Science报道SWI/SNF染色质重塑复合物决定了以T淋巴细胞为基础的免疫治疗的效果。本课题组较早关注并系统研究了SWI/SNF核心亚基BRM在ccRCC中的缺失现象及临床意义，发现BRM缺失型ccRCC被大量杀伤性T细胞（CTL）包绕，理论上易受生物体免疫系统杀伤清除，与其临床不良预后存在显著矛盾，推测BRM缺失型ccRCC存在免疫麻痹现象。STING是新近发现的调控宿主免疫应答与耐受的关键介质。基于此，本项目拟利用已具备的基因工程小鼠与细胞平台，论证如下假说：BRM原发性缺失造成ccRCC基因组稳定性降低，激活STING通路，上调肿瘤细胞PD-L1表达水平，从而抑制CTL效能，实施免疫逃逸，最终导致其预后不良。本项目有助于精准调控ccRCC肿瘤免疫微环境，为新型免疫治疗靶点提供理论依据。

Immunothrapy plays a pivotal role in the management of clear cell renal cell carcinoma (ccRCC) that shows low sensitivities to traditional anti-tumor therapy. Recent reports suggest that SWI/SNF complex correlates with the effect of immunotherapy in ccRCC, although the underlying mechanism is unclear yet. Our previous studies have demonstrated that loss of BRM is associated with aggregated cytotoxic T lymphocytes (CTL), which is in conflict with the poor prognosis of BRM-deficient ccRCC. We therefore speculate an immune paralysis in BRM-deficient ccRCC. STING is a recently identified controller in host immune response and tolerance. In this study, we will utilize STING-deficient mice and BRM-deficient/over-expressed cell lines to demonstrate the underlying mechanism by which SWI/SNF subunit BRM regulates CTL via STING signaling in ccRCC. This study will help to understand the microenvironment and provide potential new immune targets in the treatment of ccRCC.