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.
英文原题:Combined modality including novel sensitizers in gynecological cancers.
Combined modality including novel sensitizers in gynecological cancers.
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局部晚期妇科癌症的标准治疗主要依赖以铂类为基础的同步放化疗,随后进行近距离放疗。目前的化疗药物仅具有短暂疗效,晚期疾病患者尽管原发肿瘤初期反应显著,但往往产生耐药并随后发生远处转移。
此外,部分患者仍出现局部失败或进展,提示仍有提高抗肿瘤放射效应的空间。目前正在开发多种策略以提高治愈患者的概率。阴道癌和外阴癌是罕见疾病,其组织学和发病机制与宫颈癌相似。这些妇科癌症主要与人乳头瘤病毒感染相关。其他不可切除妇科癌症的治疗策略通常来源于局部晚期宫颈癌的证据。在本综述中,我们基于临床前及正在进行的临床数据,讨论新型疗法如何与常规放化疗产生协同作用的机制。目前临床试验正在测试三联、甚至四联治疗模式。源自转移性治疗背景并正在局部晚期肿瘤中测试的新型联合方案包括抗血管生成药物、免疫治疗、TIL 治疗、过继性 T 细胞治疗和凋亡诱导剂,通过互补的分子通路增强放化疗疗效。与此同时,放射增敏剂,如纳米颗粒和乏氧放射增敏剂,旨在最大化局部放疗效果。
Standard treatment of locally advanced gynecological cancers relies mainly on platinum-based concurrent chemoradiotherapy followed by brachytherapy. Current chemotherapeutic drugs are only transiently effective and patients with advanced disease often develop resistance and subsequently, distant metastases despite significant initial responses of the primary tumor.
In addition, some patients still develop local failure or progression, suggesting that there is still a place for increasing the anti-tumor radiation effect. Several strategies are being developed to increase the probability of curing patients. Vaginal cancer and vulva cancer are rare diseases, which resemble cervical cancer in their histology and pathogenesis. These gynecological cancers are predominantly associated with human papilloma virus infection. Treatment strategies in other unresectable gynecologic cancers are usually derived from evidence in locally advanced cervical cancers.
In this review, we discuss mechanisms by which novel therapies could work synergistically with conventional chemoradiotherapy, from pre-clinical and ongoing clinical data. Trimodal, even quadrimodal treatment are currently being tested in clinical trials.
Novel combinations derived from a metastatic setting, and being tested in locally advanced tumors, include anti-angiogenic agents, immunotherapy, tumor-infiltrating lymphocytes therapy, adoptive T-cell therapy and apoptosis inducers to enhance chemoradiotherapy efficacy through complementary molecular pathways. In parallel, radiosensitizers, such as nanoparticles and radiosensitizers of hypoxia aim to maximize the effect of radiotherapy locally.
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