DAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong China.
Department of Surgery, UT Southwestern Medical Center, Dallas, Texas USA.
Oncoimmunology. 2022 Apr 25;11(1):2068488. doi: 10.1080/2162402X.2022.2068488. eCollection 2022.
Interferon gamma (IFNG/IFNγ)-induced adaptive immune resistance remains a challenge for tumor therapy. We observed that the chaperone heat shock protein 90 (HSP90) stabilizes the transcription factor signal transducer and activator of transcription 1 (STAT1), resulting in IFNγ-induced expression of immunosuppressive indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1/CD274). Pharmacological inhibition of HSP90 enhances the efficacy of programmed cell death 1 (PDCD1/PD-1) targeting immunotherapy in suitable mouse models without any toxicity.
干扰素 γ（IFNG/IFNγ）诱导的适应性免疫抵抗仍然是肿瘤治疗的一个挑战。我们观察到伴侣热休克蛋白 90（HSP90）稳定转录因子信号转导和转录激活因子 1（STAT1），导致 IFNγ 诱导的免疫抑制吲哚胺 2,3-双加氧酶 1（IDO1）和程序性死亡配体 1（PD-L1/CD274）的表达。HSP90 的药理学抑制增强了合适的小鼠模型中针对程序性细胞死亡 1（PDCD1/PD-1）的靶向免疫疗法的疗效，而没有任何毒性。
