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:Galectin-9, a pro-survival factor inducing immunosuppression, leukemic cell transformation and expansion.
Galectin-9, a pro-survival factor inducing immunosuppression, leukemic cell transformation and expansion.
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白血病是一种起源于自我更新的癌性未成熟原始细胞或转化白细胞的骨髓和血液恶性肿瘤。尽管治疗有所改善,但由于疾病异质性、耐药性和复发,白血病仍然是一种预后不良的严重疾病。新出现的证据表明,共信号分子的差异表达在肿瘤免疫逃逸中起关键作用。Galectin-9(Gal-9)是白血病细胞表达、分泌并用于增殖、自我更新和存活的关键蛋白之一。它还抑制由 T 和 NK 细胞控制的宿主免疫反应,使白血病细胞能够逃避免疫监视。本综述提供了 Gal-9 诱导白血病免疫逃逸的分子机制。理解由表达 Gal-9 的白血病细胞驱动的复杂免疫逃逸机制,将有助于确定对白血病患者进行有效免疫治疗的新治疗策略。可以考虑针对 T 细胞免疫球蛋白和黏蛋白结构域-3(Tim-3)/Gal-9 及其他免疫检查点通路的联合治疗方法,这可能增强宿主效应细胞攻击白血病细胞的疗效。
Leukemia is a malignancy of the bone marrow and blood originating from self-renewing cancerous immature blast cells or transformed leukocytes. Despite improvements in treatments, leukemia remains still a serious disease with poor prognosis because of disease heterogeneity, drug resistance and relapse. There is emerging evidence that differentially expression of co-signaling molecules play a critical role in tumor immune evasion. Galectin-9 (Gal-9) is one of the key proteins that leukemic cells express, secrete, and use to proliferate, self-renew, and survive.
It also suppresses host immune responses controlled by T and NK cells, enabling leukemic cells to evade immune surveillance. The present review provides the molecular mechanisms of Gal-9-induced immune evasion in leukemia. Understanding the complex immune evasion machinery driven by Gal-9 expressing leukemic cells will enable the identification of novel therapeutic strategies for efficient immunotherapy in leukemic patients.
Combined treatment approaches targeting T-cell immunoglobulin and mucin domain-3 (Tim-3)/Gal-9 and other immune checkpoint pathways can be considered, which may enhance the efficacy of host effector cells to attack leukemic cells.
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