单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Navigating the landscape of immune checkpoint inhibitors and novel immunotherapies in melanoma: long-term outcomes, progress, and challenges.
Navigating the landscape of immune checkpoint inhibitors and novel immunotherapies in melanoma: long-term outcomes, progress, and challenges.
将新型预后和预测生物标志物整合到个性化医疗中,是未来的方向,不仅可用于优化患者筛选和治疗选择,还可用于确定治疗和监测的持续时间,从而实现早期复发检测,并获得TIL(肿瘤浸润淋巴细胞)等更新疗法,以最大化黑色素瘤患者的治愈比例。需要进一步研究优化ICI和其他免疫治疗的毒性管理,包括减少类固醇暴露以改善患者结局并维持生活质量。
过去10-15年间,免疫治疗的应用使黑色素瘤成为晚期恶性肿瘤中取得变革性疗效的典范,中位生存期从约1年提高到超过5年。随着免疫检查点抑制剂(ICI)及其他新型免疫治疗方法的不断增加,整合和序贯治疗以创建新范式已日益受到重视,重点关注优化毒性管理以及免疫治疗耐药、脑转移、生育力和随访持续时间等复杂场景。涵盖领域:在本综述中,我们总结了迄今为止黑色素瘤治疗的进展和新出现的证据,并探讨了改善上述特定患者群体结局的管理策略和可能的未来方向。
INTRODUCTION: Melanoma has become the poster child for transformative outcomes in advanced malignancy from the use of immunotherapy over the last 10-15 years with median survival improving from ~ 1 to > 5 years. With the increasing repertoire of immune checkpoint inhibitors (ICI) and other novel immunotherapeutic approaches, integrating and sequencing treatments to create new paradigms has gained prominence, with focus on optimizing toxicity management and complex scenarios such as immunotherapy resistance, brain metastases, fertility, and duration of follow-up. AREAS COVERED: In this review, we summarize the progress and emerging evidence in melanoma treatments to date and consider management and possible future directions to improve outcomes for above-mentioned specific patient cohorts. EXPERT OPINION: Personalized care with integration of novel prognostic and predictive biomarkers is the way forward in tailoring not only patient selection and choice of therapy, but also duration of treatment and surveillance to allow for early recurrence detection and access to newer therapies such as tumor infiltrating lymphocytes (TIL) to maximize the curative fraction of melanoma patients. Further research is needed in optimizing ICI and other immunotherapy toxicity management, including reducing steroid exposure for better patient outcomes and preserving quality of life.
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