下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Immunotherapy for high-grade endometrial stromal sarcoma: a narrative review bridging molecular insights to clinical translation.
高级别子宫内膜间质肉瘤(HGESS)是一种罕见的实体恶性肿瘤,以预后差和高度侵袭性行为为特征。
高级别子宫内膜间质肉瘤(HGESS)是一种罕见的实体恶性肿瘤,以预后差和高度侵袭性为特征。目前,手术切除仍是HGESS的主要治疗方法。放疗和化疗可以解决局部症状并提高患者的生活质量;然而,它们并不能提高患者的生存率。近年来的研究发现,HGESS的分子特征(如YWHAE-NUTM2、ZC3H7B-BCOR等基因融合)驱动了肿瘤的高侵袭性。尽管免疫治疗在实体瘤中取得了重大突破,但HGESS的免疫抑制微环境仍是未来免疫治疗研究的关键焦点。本叙述性综述全面分析了HGESS中肿瘤微环境改变与免疫逃逸机制之间的相互作用。同时提出了多种免疫治疗选择,包括溶瘤病毒治疗、过继性细胞转移治疗、免疫检查点抑制剂、癌症疫苗及联合策略。我们认为,深入理解HGESS的分子免疫学特征、识别有效的生物标志物以及实施设计良好的临床研究,是将免疫治疗成功转化为这一难治性HGESS有效治疗不可或缺的途径。
High-grade endometrial stromal sarcoma (HGESS) is a rare solid malignancy characterized by a poor prognosis and highly aggressive behavior. Currently, surgical resection remains the primary treatment for HGESS. Radiotherapy and chemotherapy can address local symptoms and enhance the quality of life of patients; however, they do not improve patient survival rates. Recent studies have found that the molecular characteristics of HGESS (such as gene fusions like YWHAE-NUTM2, ZC3H7B-BCOR, etc.) drive the high invasiveness of the tumor. Although immunotherapy has achieved significant breakthroughs in solid tumors, the immunosuppressive microenvironment of HGESS remains a key focus for future immunotherapy research. This narrative review comprehensively analyzes the interactions between alterations in the tumor microenvironment and immune escape mechanisms in HGESS. It also proposes a diverse range of immunotherapy options, including Oncolytic virus therapy, adoptive cell transfer therapy, immune checkpoint inhibitors, cancer vaccines, and combination strategies. We hold the view that a profound comprehension of the molecular immunological characteristics of HGESS, the identification of effective biomarkers, and the implementation of well-designed clinical studies are the indispensable routes to successfully translate immunotherapy into an effective treatment for this intractable HGESS.
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