为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).
Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
肝脏移植肿瘤学(TO)是一个临床和科学关注度日益增加的领域,涵盖了一组异质性的临床-病理情况。LT后的免疫抑制管理是影响结果的关键因素。
然而,针对疾病的相关指导仍然缺乏,该领域仍存在许多未解决的问题。基于如此缺乏坚实证据的现状,意大利肝移植专家委员会(I-BELT)(一个包括所有国内移植中心代表的工作组)首次推动了关于该主题的方法学严谨的共识会议,基于GRADE方法。本文呈现并评论了该工作组的最终建议。18个PICO和声明及其证据水平和推荐等级被报告并归为七个领域:(1)通过组织病理学和生物分子参数进行风险分层以及mTORi在LT后的作用;(2)类固醇与HCC复发;(3)LT后HCC复发时免疫抑制的管理;(4)mTORi单药治疗;(5)机器灌注与LT后HCC复发;(6)TIL(肿瘤浸润淋巴细胞)的病理生理学与免疫抑制,炎症的作用;(7)肝移植患者的免疫治疗。对哺乳动物雷帕霉素靶蛋白抑制剂(mTORi)的兴趣、避免使用类固醇以及减少CNI暴露的需求从共识过程中浮现。还制定了一份精选的未满足需求清单,以促进进一步研究。迄今为止,肿瘤患者免疫抑制的异质性和碎片化方法值得付出更大努力,以对不同临床场景实现更标准化的治疗反应。这一共识过程朝着这个方向迈出了前所未有的第一步,有待在更大规模上发展。
Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result.
However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients.
The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed.
The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.
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