免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Melanoma 3.0T-Tech Innovations, New Targeted Therapies, and T-Cell Breakthroughs.
Melanoma 3.0T-Tech Innovations, New Targeted Therapies, and T-Cell Breakthroughs.
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新技术和创新正在改变黑色素瘤治疗的未来。远程皮肤病学和皮肤筛查移动应用程序在人工智能(AI)诊断支持下,可能有助于弥合黑色素瘤早期检测和获得专科治疗方面的差距。尽管过去十年皮肤病学AI领域发展迅猛,但使用真实世界多模态数据集对现有算法进行前瞻性验证显示性能下降,限制了其目前在临床实践中的应用。较新的方法学方法聚焦于AI如何增强临床决策以加速诊断和医疗服务提供——以及模型输出结果是否能为患者带来有利变化。选择性BRAF和MEK抑制剂在辅助治疗和转移性治疗中已确立作用,适用于约50%的黑色素瘤携带BRAF V600突变的患者。
然而,对这些药物的获得性耐药仍是一个挑战。对于其他驱动突变,包括II类和III类BRAF突变、NRAS和CDKN2A改变,新型药物和联合方案正在展现出有前景的活性。至少50%的转移性黑色素瘤患者无法从免疫检查点抑制剂(ICIs)中获得长期获益。采用TIL(肿瘤浸润淋巴细胞)的过继性细胞免疫治疗为其中少数患者提供了持久缓解的可能性。可能更有效且耐受性更好的T细胞疗法正在临床试验中进行评估。
New technologies and innovations are changing the future of melanoma care. Teledermatology and skin screening mobile apps aided by artificial intelligence (AI) diagnostic support could assist in closing disparity gaps in melanoma early detection and access to specialty care. Although the field of AI in dermatology has exploded over the past decade, prospective validation of available algorithms using real-world, multimodal data sets has shown performance decline, limiting their current use in clinical practice. Newer methodological approaches have focused on how AI can augment clinical decision making to speed diagnosis and care delivery-and whether the model output results in a favorable change for the patient.
Selective BRAF and MEK inhibitors have an established role in the adjuvant and metastatic setting for the approximately 50% of patients whose melanomas harbor a BRAF V600 mutation. Acquired resistance to these agents remains a challenge, however. For other driver mutations, including class II and III BRAF mutations, alterations in NRAS and CDKN2A, novel agents and combinations are demonstrating promising activity.
At least 50% of patients with metastatic melanoma do not derive long-term benefit from immune checkpoint inhibitors (ICIs). Adoptive cellular immunotherapy with tumor infiltrating lymphocytes offers the possibility of a durable response for a minority of these patients. Potentially more effective and better tolerated T-cell therapies are being evaluated in clinical trials.
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