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:Precision Oncology in Melanoma: Changing Practices.
Precision Oncology in Melanoma: Changing Practices.
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在过去20年中,我们对恶性黑色素瘤的基因组学、肿瘤免疫微环境及免疫原性的认识取得了显著进展。历史上,由于治疗选择有限,转移性黑色素瘤的预后较差。
然而,在多项具有里程碑意义的临床试验证实了BRAF/MEK联合抑制对BRAF突变黑色素瘤的疗效,以及靶向程序性死亡受体-1、细胞毒性T淋巴细胞抗原-4和淋巴细胞激活基因-3分子的免疫检查点抑制剂的应用之后,总生存率已显著提高。此后,免疫检查点抑制的作用已扩展至新辅助和辅助治疗领域,多种方案已进入常规使用。个体化疗法显示出前景,包括从患者黑色素瘤中提取并最终回输至患者体内的TIL(肿瘤浸润淋巴细胞),以及用于靶向患者肿瘤所特有新抗原的信使RNA疫苗。伴随影像学手段的进步,尤其是核医学领域的进展,使疾病的分期更加准确,并能更好地评估治疗反应。预计在未来几年,核医学在黑色素瘤评估中的作用将持续扩大,包括将人工智能纳入影像判读,以及使用放射性标记示踪剂实现对肿瘤免疫微环境的精细成像。
Over the last 2 decades, significant progress has been made in our understanding of the genomics, tumor immune microenvironment, and immunogenicity of malignant melanoma. Historically, the prognosis for metastatic melanoma was poor because of limited treatment options.
However, after multiple landmark clinical trials displaying the efficacy of combined BRAF/MEK inhibition for BRAF -mutant melanoma and the application of immune checkpoint inhibitors targeting the programmed death-1, cytotoxic T-lymphocyte antigen-4, and lymphocyte activation gene-3 molecules, overall survival rates have dramatically improved. The role of immune checkpoint inhibition has since expanded to the neoadjuvant and adjuvant settings with multiple regimens in routine use.
Personalized therapies, including tumor-infiltrating lymphocytes that are extracted from a patient's melanoma and eventually reinfused into the patient, and messenger RNA vaccines used to target neoantigens unique to a patient's tumor, show promise. Improvements in accompanying imaging modalities, particularly within the field of nuclear medicine, have allowed for more accurate staging of disease and assessment of treatment response.
Continued growth in the role of nuclear medicine in the evaluation of melanoma, including the incorporation of artificial intelligence into image interpretation and use of radiolabeled tracers allowing for intricate imaging of the tumor immune microenvironment, is expected in the coming years.
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