TRx0237 induces apoptosis and enhances anti-PD-1 immunotherapeutic efficacy in anaplastic thyroid Cancer

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-04-10 DOI:10.1016/j.intimp.2025.114610

Qingyang Ning , Jiaye Liu , Shijing Liu , Quanqing Zou , Kewei Li , Zhihui Li

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引用次数: 0

Abstract

Anaplastic thyroid cancer (ATC) is a highly malignant and lethal tumor with poor prognosis, but there is a lack of effective treatment strategies. In our study, we screened a drug library and identified that TRx0237, a tau protein inhibitor, showed inhibitory effect on ATC cells. Further research demonstrated that the inhibitory effect of TRx0237 was mainly through the induction of apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum stress pathway. Meanwhile, the pro-apoptosis effect and mechanism of TRx0237 on ATC were verified in xenograft and ATC patient-derived organoids. In addition, TRx0237 significantly upregulated the expression of PD-L1 in ATC, and synergistically enhanced the effect of anti-PD-1 therapy in xenograft and organoids model. Therefore, our study suggests that TRx0237 showed anticancer effects by inducing apoptosis and improving the efficacy of anti-PD-1 immunotherapy. TRx0237 is a potential agent for the treatment of ATC.

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甲状腺无节细胞癌（ATC）是一种高度恶性的致死性肿瘤，预后较差，但目前缺乏有效的治疗策略。在我们的研究中，我们对药物库进行了筛选，发现一种 tau 蛋白抑制剂 TRx0237 对 ATC 细胞有抑制作用。进一步的研究表明，TRx0237的抑制作用主要是通过活性氧（ROS）介导的内质网应激途径诱导细胞凋亡。同时，在异种移植和ATC患者衍生的器官组织中验证了TRx0237对ATC的促凋亡作用及其机制。此外，TRx0237还能显著上调PD-L1在ATC中的表达，并在异种移植和器官组织模型中协同增强抗PD-1治疗的效果。因此，我们的研究表明，TRx0237通过诱导细胞凋亡和提高抗PD-1免疫疗法的疗效而显示出抗癌作用。TRx0237是一种治疗ATC的潜在药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.