RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression.
Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression.
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TIL(肿瘤浸润淋巴细胞)是肿瘤微环境的重要组成部分。数十年来,TIL在肿瘤生长和进展中的作用一直存在争议。目前研究重点已转向TIL对宿主的有益作用,以及通过减轻肿瘤微环境中的免疫抑制来优化其获益的治疗。证据表明,当肿瘤中存在由活化免疫细胞构成的高密度TIL聚集时,肿瘤预后和治疗应答较好。群体水平及单细胞水平的TIL基因特征和蛋白质谱,不仅可揭示其表型和数量,也可提示其在肿瘤中的潜在功能。将TIL数据与肿瘤临床病理特征、临床结局和患者生存进行关联分析表明,TIL可影响疾病进展,尤其是在结直肠癌和乳腺癌中。
同时,人们认识到TIL特征会随时间和癌症进展而变化,由此开始研究TIL作为潜在预后生物标志物的价值。肿瘤可利用多种机制破坏宿主免疫系统。TIL促肿瘤与抗肿瘤应答之间的平衡,很大程度上取决于每位癌症患者独特的肿瘤微环境。这种平衡由肿瘤主导,因此偏向促进肿瘤生长。肿瘤进展期间TIL发生的变化似乎可衡量肿瘤侵袭性,并可能成为选择治疗策略和判断预后的关键依据。
Tumor-infiltrating lymphocytes (TIL) are an important component of the tumor environment. Their role in tumor growth and progression has been debated for decades. Today, emphasis has shifted to beneficial effects of TIL for the host and to therapies optimizing the benefits by reducing immune suppression in the tumor microenvironment. Evidence indicates that when TILs are present in the tumor as dense aggregates of activated immune cells, tumor prognosis and responses to therapy are favorable. Gene signatures and protein profiling of TIL at the population and single-cell levels provide clues not only about their phenotype and numbers but also about TIL potential functions in the tumor.
Correlations of the TIL data with clinicopathological tumor characteristics, clinical outcome, and patients' survival indicate that TILs exert influence on the disease progression, especially in colorectal carcinomas and breast cancer. At the same time, the recognition that TIL signatures vary with time and cancer progression has initiated investigations of TIL as potential prognostic biomarkers. Multiple mechanisms are utilized by tumors to subvert the host immune system.
The balance between pro- and antitumor responses of TIL largely depends on the tumor microenvironment, which is unique in each cancer patient. This balance is orchestrated by the tumor and thus is shifted toward the promotion of tumor growth. Changes occurring in TIL during tumor progression appear to serve as a measure of tumor aggressiveness and potentially provide a key to selecting therapeutic strategies and inform about prognosis.
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