肿瘤细胞治疗研究
英文原题：Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma.
胆管细胞癌（CCA）的发病率在全球范围内呈上升趋势。
胆管细胞癌（CCA）的发病率在全球范围内呈上升趋势。由于CCA缺乏特异性早期症状或特异性标志物，往往在晚期不可手术阶段才被诊断。越来越多的证据强调放射治疗在诱导抗肿瘤免疫中的重要性。细胞外囊泡（EVs）的表面蛋白组成与来源细胞相关，因此可能在囊泡功能中发挥作用。我们评估了不可手术CCA患者在接受选择性内放射治疗（SIRT）前后EVs的免疫特征及其免疫来源。共纳入47例接受SIRT的CCA患者和12名健康志愿者（HV）。分别在治疗前（pre T）和治疗后（after T）采血。通过分化簇（CD）9、CD63和CD81免疫磁珠分离法从血浆中纯化EVs。为检测差异丰度的表面标志物，评估了动态范围和EVs输入质量。通过流式细胞术检测了共37种EVs表面标志物，并将其与给药活度剂量（MBq）或至死亡间隔时间（月）进行相关性分析。EVs表型分析鉴定出淋巴细胞、B细胞、NK细胞、血小板、内皮细胞、白细胞活化、B细胞活化、T细胞和B细胞黏附标志物、干细胞/祖细胞以及抗原提呈细胞（APC）作为EVs的亲代细胞。与HV相比，CCA患者pre T时CD4和CD8显著下降，而其他标志物显著升高。血小板来源的EVs显著减少，在SIRT后恢复至HV水平，但与HV相比仍显著升高。B细胞来源的EVs在pre T时较HV显著增加，且与给药活度剂量呈正相关。MHCII和CD40 EVs显著增加了pre SIRT，并与给药活度剂量呈负相关，而来自抗原呈递细胞的EVs和CD49e pre SIRT与治疗后生存时间呈正相关。癌症pre T中CD24和CD44水平升高，在post T中显著降低。在已证实的EVs异质性中，特别是B细胞来源、MHCII和CD40阳性或APC来源的EVs，需要进一步研究其在临床场景中的诊断或预后相关性。
The incidence of cholangiocellular carcinoma (CCA) is rising worldwide. As there are no specific early symptoms or specific markers of CCA, it is often diagnosed in later inoperable stages. Accumulating evidence underlines the importance of radiation therapy in the induction of antitumor immunity. The surface protein composition on extracellular vesicles (EVs) relates to originating cells and thus may play a role in vesicle function. We assessed immune profiles of EVs and their immune origin in patients with inoperable CCA prior and after selective internal radiotherapy (SIRT). A total of 47 CCA patients receiving SIRT and 12 healthy volunteers (HV) were included. Blood was withdrawn before therapy (pre T) and after T. EVs were purified from plasma by cluster of differentiation (CD)9-, CD63-, and CD81-immunobead isolation. To detect differently abundant surface markers, dynamic range and EVs input quality were assessed. A total of 37 EVs surface markers were measured by flow cytometry and correlated either with the administered activity dose (MBq) or with the interval until death (month). EVs phenotyping identified lymphocytes, B cells, NK cells, platelets, endothelial cells, leukocyte activation, B cell activation, T and B cell adhesion markers, stem/progenitor cells, and antigen-presenting cells (APC) as EVs-parenteral cells. CD4 and CD8 significantly declined, while other markers significantly increased in CCA patients pre T vs. HV. Platelets-deriving EVs significantly decreased, normalizing to levels of HV but still significantly increasing vs. HV post SIRT. B cells-deriving EVs significantly increased pre T vs. HV, positively correlating with administered activity dose. MHCII and CD40 EVs significantly increased pre SIRT and negatively correlated with administered activity dose, while EVs from antigen presenting cells and CD49e pre SIRT positively correlated with survival time after therapy. Increased levels of CD24 and CD44 in cancer pre T were significantly decreased post T. Among the heterogeneity of EVs that was demonstrated, in particular, B cells-deriving, MHCII, and CD40 positive or APC-deriving EVs need to be further studied for their diagnostic or prognostic relevance in clinical scenarios.
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