肿瘤细胞治疗研究
英文原题：The role of tumor-infiltrating lymphocytes in cholangiocarcinoma.
TIL的存在可能是预后和新型治疗潜在靶点的重要标志物，但需要更多的临床和转化数据来充分揭示TIL在CCA治疗中的重要性。
胆管癌（CCA）是第二常见的原发性肝癌，由于缺乏有效的全身治疗，其预后极差。与其他癌症相比，新的免疫疗法在临床试验中显示出令人不满意的结果，这凸显了深入了解CCA特殊肿瘤微环境以及与肿瘤相互作用的免疫细胞作用的重要性。TIL（肿瘤浸润淋巴细胞）（TILs）是适应性免疫系统的重要组成部分，也是当前免疫疗法的基础。因此，本系统综述的目的是总结当前文献，重点关注CCA患者中TILs的比例与分布、分子发病机制、预后意义及其在免疫治疗中的作用。在CCA中，CD8+和CD4+ T淋巴细胞占TILs的大多数，且大多隔离在癌细胞周围。CD20+ B淋巴细胞和自然杀伤（NK）细胞较少见。相反，Foxp3+细胞（调节性T细胞，Tregs）被观察到浸润到肿瘤中。在CCA的免疫微环境中，癌细胞和基质细胞如TAMs、TANs、MSDCs和CAFs通过分泌IL-10和TGF-等因子抑制TILs的免疫保护功能。在分子发病机制方面，Wnt/-catenin、TGF-信号通路、aPKC-i/P-Sp1/Snail信号、B7-H1/PD-1通路和Fas/FasL信号通路与恶性潜能相关，并通过增加TIL凋亡促进肿瘤免疫逃逸。不同亚型的TILs对CCA的长期预后显示出不同的预后意义。尽管偶尔存在矛盾的结果，但CD8+和CD4+T细胞以及CD20+B细胞与CCA的肿瘤学预后呈正相关，而高数量的Tregs很可能与较差的总生存期相关。TILs在CCA的免疫治疗中也发挥重要作用。总之，TILs的存在可能代表预后的重要标志物和新型治疗的潜在靶点，但需要更多的临床和转化数据来充分揭示TILs在CCA治疗中的重要性。
Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients.In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF- . With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA.In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translationaldata is needed to fully unravel the importance of TILs in the treatment of CCA.
MEMBER ACCOUNT
登录成功会直接打开下一页。
