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胃肠神经内分泌肿瘤免疫治疗策略的演变

英文原题:Evolving Immunotherapy Strategies in Gastrointestinal Neuroendocrine Neoplasms.

PubMed 2025/01/23(内容时间) Curr Treat Options Oncol Q1 · IF 5.8(JCR 2025)

研究概要

神经内分泌肿瘤(NENs)的治疗根据肿瘤的原发部位、分级和分化程度进行个体化制定。

中文摘要

神经内分泌肿瘤(NENs)的治疗根据肿瘤的原发部位、分级和分化程度进行个体化制定。NENs 分为两种主要类型:分化良好的神经内分泌瘤(NETs),通常生长较慢、侵袭性较低;以及分化差的神经内分泌癌(NECs),具有高度侵袭性且更难治疗。NETs 的治疗选择包括生长抑素类似物和 mTOR 抑制剂,以及使用 Lutetium-177 dotatate 的肽受体放射性核素治疗(PRRT)。在疾病进展较快的情况下,也可考虑细胞毒性化疗。相比之下,化疗在 NECs 的治疗中发挥核心作用,通常采用与小细胞肺癌类似的方案。NENs 新疗法的开发正在取得令人振奋的进展。受免疫治疗在其他癌症中取得成功的启发,临床试验已开始探索其在 NENs 中的潜力。早期研究结果表明,免疫检查点抑制剂(ICIs)可能带来获益,尤其是在较高分级的 NETs 和 NECs 患者中。然而,由于 NENs 具有免疫学上“冷”的肿瘤微环境——意味着它们较不可能触发免疫反应——因此需要新的策略来增强 ICI 的疗效。为克服这一挑战,研究人员正在探索创新方法,例如联合使用双重 ICIs 或将 ICIs 与其他治疗药物配对,以使肿瘤对免疫攻击更敏感。此外,人们对旨在增强免疫系统识别和摧毁癌细胞能力的尖端疗法热情日益高涨。这些疗法包括双特异性 T 细胞衔接器、CAR-T 细胞、TIL(肿瘤浸润淋巴细胞)、溶瘤病毒和癌症疫苗。虽然它们在 NENs 中的有效性仍在研究中,但这些方法具有相当大的前景,为这种具有挑战性和复杂性的癌症类型患者带来了新的希望。

展开英文摘要原文

Treatment for neuroendocrine neoplasms (NENs) is tailored to the tumor's site of origin, grade, and differentiation. NENs are categorized into two main types: well-differentiated neuroendocrine tumors (NETs), which tend to grow more slowly and are less aggressive, and poorly differentiated neuroendocrine carcinomas (NECs), which are highly aggressive and harder to treat. Treatment options for NETs range from somatostatin analogues and mTOR inhibitors to peptide receptor radionuclide therapy (PRRT) with Lutetium-177 dotatate. In cases where the disease progresses more rapidly, cytotoxic chemotherapy may also be considered. In contrast, chemotherapy plays a central role in treating NECs, often following protocols similar to those used for small cell lung cancer. Exciting progress is being made in the development of new therapies for NENs. Inspired by the success of immunotherapy in other cancers, clinical trials have begun to explore its potential in NENs. Early findings suggest that immune checkpoint inhibitors (ICIs) may offer benefits, especially in patients with higher-grade NETs and NECs. However, because NENs have an immunologically "cold" tumor microenvironment-meaning they are less likely to trigger an immune response-new strategies are needed to boost ICI efficacy. To overcome this challenge, researchers are exploring innovative approaches, such as combining dual ICIs or pairing ICIs with other therapeutic agents to make the tumors more responsive to immune attack. Moreover, there is growing enthusiasm for cutting-edge therapies designed to enhance the immune system's ability to recognize and destroy cancer cells. These include bispecific T cell engagers, chimeric antigen receptor T cells, tumor-infiltrating lymphocytes, oncolytic viruses, and cancer vaccines. While their effectiveness in NENs is still being studied, these approaches hold considerable promise, offering new hope for patients with this challenging and complex cancer type.

论文信息

作者
Urman A、Schonman I、De Jesus-Acosta A
第一作者单位
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.United States
通讯作者单位
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. adejesu1@jhmi.edu.United States
文献类型
综述
期刊
Current treatment options in oncology2025 Feb
原文标识
PubMed 39843688 · DOI 10.1007/s11864-024-01283-4