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:Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 2nd - 4th, 2021, Italy).
Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 2nd - 4th, 2021, Italy).
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免疫检查点及联合治疗的进展改善了晚期黑色素瘤患者的总生存期。对肿瘤、肿瘤微环境及肿瘤免疫逃逸机制认识的深入,促成了靶向和利用宿主免疫应答的新方法。联合其他免疫治疗药物、化疗、放疗、电化疗的综合模式也正在探索中,以克服耐药并增强免疫应答。
此外,过继细胞治疗、溶瘤病毒、疫苗以及包括序贯治疗或联合治疗在内的不同给药策略等新方法也正在接受测试。尽管在黑色素细胞病变的诊断方面取得了进展,但患者的正确分类、适当辅助治疗和全身治疗的选择以及治疗反应的预测,仍然是黑色素瘤面临的现实挑战。对肿瘤微环境、肿瘤免疫及治疗反应认识的提高,推动了黑色素瘤领域广泛的转化研究和临床研究。越来越多的证据表明,治疗前肿瘤活检的基因组和免疫特征可能与黑色素瘤及其他癌症患者的治疗反应相关,但这些特征尚未被充分表征并在临床中应用。新型生物标志物平台的开发可能有助于改进诊断和预测准确性,从而为特定治疗选择患者。
总体而言,黑色素瘤治疗和转化研究的未来研究方向应聚焦于以下几个方面:(a) 开发稳健的生物标志物以预测治疗方式的疗效,从而指导临床决策和优化治疗方案,(b) 识别免疫检查点抑制剂治疗耐药的机制,这些机制可能具有可干预性,(c) 识别预测治疗诱导不良事件的生物标志物,以及 (d) 研究治疗药物的作用机制并开发优化联合治疗的算法。在 Melanoma Bridge 会议(2021年12月2日至4日,意大利那不勒斯)期间,讨论聚焦于目前已获批用于晚期黑色素瘤的系统性和局部治疗,并探讨了新型生物标志物策略和精准医学的进展,以及 COVID-19 疫情对黑色素瘤患者管理的影响。
Advances in immune checkpoint and combination therapy have led to improvement in overall survival for patients with advanced melanoma. Improved understanding of the tumor, tumor microenvironment and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. Combination modalities with other immunotherapy agents, chemotherapy, radiotherapy, electrochemotherapy are also being explored to overcome resistance and to potentiate the immune response.
In addition, novel approaches such as adoptive cell therapy, oncogenic viruses, vaccines and different strategies of drug administration including sequential, or combination treatment are being tested. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic theràapies, and prediction of response to therapy remain real challenges in melanoma.
Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers, but they have yet to be fully characterized and implemented clinically. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment.
Overall, the future research efforts in melanoma therapeutics and translational research should focus on several aspects including: (a) developing robust biomarkers to predict efficacy of therapeutic modalities to guide clinical decision-making and optimize treatment regimens, (b) identifying mechanisms of therapeutic resistance to immune checkpoint inhibitors that are potentially actionable, (c) identifying biomarkers to predict therapy-induced adverse events, and (d) studying mechanism of actions of therapeutic agents and developing algorithms to optimize combination treatments.
During the Melanoma Bridge meeting (December 2nd-4th, 2021, Naples, Italy) discussions focused on the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine as well as the impact of COVID-19 pandemic on management of melanoma patients.
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