CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Harnessing the immune responses: a new frontier in Ewing sarcoma treatment.
Harnessing the immune responses: a new frontier in Ewing sarcoma treatment.
尤因肉瘤(ES)是一种罕见且高度侵袭性的骨与软组织恶性肿瘤,主要影响儿童和年轻成人。
Ewing肉瘤(ES)是一种罕见且高度侵袭性的骨与软组织恶性肿瘤,主要影响儿童和年轻成人。由于其易发生转移且对传统疗法具有耐药性,该病在治疗方面面临重大挑战。尽管包括化疗、手术和放疗在内的多模式治疗取得了进展,但转移性或复发性疾病患者的预后仍然不佳。因此,迫切需要新的治疗策略。其中,基于免疫的疗法已成为一个前景广阔的前沿领域。本综述深入分析了ES当前和新兴的免疫治疗手段,包括免疫检查点抑制剂、嵌合抗原受体(CAR)T细胞疗法、工程化T细胞受体(TCR)疗法和癌症疫苗。临床前研究已证明这些策略的潜力,特别是在克服免疫逃逸和靶向肿瘤特异性抗原相关挑战方面。此外,本文讨论了肿瘤微环境中关键组分,如肿瘤相关巨噬细胞、纤维细胞和细胞外囊泡,在促进肿瘤进展和免疫抑制中的作用。本综述还重点介绍了已完成的以及正在进行的评估各种免疫疗法用于ES的临床试验,揭示了其疗效和安全性特征。尽管取得了令人鼓舞的进展,但仍存在若干障碍,包括有限的缓解率、耐药机制和不良反应。为克服这些挑战,同时靶向肿瘤及其微环境的联合疗法可能具有前景。通过总结当前进展和未来方向,本综述强调了免疫疗法改善ES患者预后的潜力。持续研究创新的免疫治疗策略对于在这种难以治疗的恶性肿瘤中实现持久缓解和长期生存至关重要。
Ewing sarcoma (ES) is a rare and highly aggressive bone and soft tissue malignancy predominantly affecting children and young adults. It poses significant challenges in treatment due to its propensity for metastasis and resistance to conventional therapies. Despite advancements in multimodal treatment, which includes chemotherapy, surgery, and radiotherapy, outcomes remain poor for patients with metastatic or recurrent disease. Therefore, novel therapeutic strategies are urgently required. Among these, immune-based therapies have emerged as a promising frontier. This review provides an in-depth analysis of current and emerging immunotherapeutic approaches in ES, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, engineered T-cell receptor (TCR) therapy, and cancer vaccines. Preclinical studies have demonstrated the potential of these strategies, particularly in overcoming challenges related to immune evasion and targeting tumor-specific antigens. Furthermore, this article discusses the role of key components in the tumor microenvironment, such as tumor-associated macrophages, fibrocytes, and extracellular vesicles, in promoting tumor progression and immune suppression. The review also highlights completed and ongoing clinical trials that evaluate various immunotherapies for ES, shedding light on their efficacy and safety profiles. Despite encouraging progress, several obstacles remain, including limited response rates, resistance mechanisms, and adverse effects. To overcome these challenges, combination therapies, targeting both the tumor and its microenvironment, may hold promise. By summarizing current advances and future directions, this review underscores the potential of immunotherapy to improve outcomes for ES patients. Continued research into innovative immune-based strategies is crucial to achieving durable responses and long-term survival in this hard-to-treat malignancy.
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