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:Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development.
Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development.
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在多种止血成分中,血小板过度活跃通过为细胞间通讯提供表面和内部成分以及表现得像免疫细胞,在癌症进展中发挥主要作用。由于血小板在稳态和疾病状态下参与并调节免疫,我们假设揭示血小板特征可能有助于构思新的基于免疫的抗癌策略。本综述的目标是汇编并讨论关于癌症相关血小板性质及其对免疫治疗干扰的最新报道。越来越多的研究强调癌细胞与血小板之间的活跃通讯,血小板促进癌细胞存活、生长和转移。血小板导向疗法的抗癌潜力已被深入研究,抗血小板药物可能预防癌症进展并改善癌症患者的生存。血小板可以(i)降低抗肿瘤活性;(ii)支持免疫调节细胞和因子的生成;(iii)促进转移,以及(iv)通过表达免疫检查点受体的配体干扰免疫治疗。肿瘤细胞诱导的血小板活化产生的介质支持静脉血栓形成,抑制抗肿瘤T细胞和NK 细胞反应,同时促进肿瘤细胞的外渗、转移潜能以及肿瘤内新生血管形成。近期研究表明,减弱免疫血栓形成、调节血小板及其因子在免疫治疗优化方面具有良好的前景。特别是,阻断肿瘤内血小板相关的程序性死亡配体 1可能促进抗肿瘤T细胞诱导的细胞毒性。
总体而言,这些发现表明血小板可能代表相关癌症分期生物标志物的来源,以及抗癌免疫治疗策略中有前景的靶点和载体。
Among multiple hemostasis components, platelets hyperactivity plays major roles in cancer progression by providing surface and internal components for intercellular crosstalk as well as by behaving like immune cells. Since platelets participate and regulate immunity in homeostatic and disease states, we assumed that revealing platelets profile might help in conceiving novel anti-cancer immune-based strategies. The goal of this review is to compile and discuss the most recent reports on the nature of cancer-associated platelets and their interference with immunotherapy. An increasing number of studies have emphasized active communication between cancer cells and platelets, with platelets promoting cancer cell survival, growth, and metastasis. The anti-cancer potential of platelet-directed therapy has been intensively investigated, and anti-platelet agents may prevent cancer progression and improve the survival of cancer patients.
Platelets can (i) reduce antitumor activity; (ii) support immunoregulatory cells and factors generation; (iii) underpin metastasis and, (iv) interfere with immunotherapy by expressing ligands of immune checkpoint receptors. Mediators produced by tumor cell-induced platelet activation support vein thrombosis, constrain anti-tumor T- and natural killer cell response, while contributing to extravasation of tumor cells, metastatic potential, and neovascularization within the tumor.
Recent studies showed that attenuation of immunothrombosis, modulation of platelets and their factors have a good perspective in immunotherapy optimization. Particularly, blockade of intra-tumoral platelet-associated programmed death-ligand 1 might promote anti-tumor T cell-induced cytotoxicity. Collectively, these findings suggest that platelets might represent the source of relevant cancer staging biomarkers, as well as promising targets and carriers in immunotherapeutic approaches for combating cancer.
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