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:The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors.
The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors.
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非经典人类白细胞抗原G(HLA-G)是一种参与诱导免疫耐受的强效调节蛋白。这是基于膜结合型和可溶性HLA-G与多种免疫效应细胞上表达的抑制性受体结合,尤其是NK细胞和T细胞,从而导致其功能减弱。尽管在生理条件下HLA-G的表达局限于免疫豁免组织,但HLA-G表达在实体和血液系统恶性肿瘤中经常被检测到,包括泌尿系统癌症,如肾细胞癌和尿路上皮膀胱癌,并且与泌尿系统癌症的进展和患者不良预后相关:HLA-G表达通过与其抑制性受体相互作用,调节免疫细胞的表型和功能,从而保护肿瘤细胞免受抗肿瘤免疫攻击,导致免疫逃逸。本综述将讨论HLA-G在泌尿系统肿瘤中表达的表达、调控、功能和临床相关性,以及其作为肾细胞癌和尿路上皮膀胱癌治疗的推定生物标志物和/或潜在治疗靶点的应用。
The non-classical human leukocyte antigen G (HLA-G) is a potent regulatory protein involved in the induction of immunological tolerance. This is based on the binding of membrane-bound as well as soluble HLA-G to inhibitory receptors expressed on various immune effector cells, in particular NK cells and T cells, leading to their attenuated functions.
Despite its restricted expression on immune-privileged tissues under physiological conditions, HLA-G expression has been frequently detected in solid and hematopoietic malignancies including urological cancers, such as renal cell and urothelial bladder carcinoma and has been associated with progression of urological cancers and poor outcome of patients: HLA-G expression protects tumor cells from anti-tumor immunity upon interaction with its inhibitory receptors by modulating both the phenotype and function of immune cells leading to immune evasion.
This review will discuss the expression, regulation, functional and clinical relevance of HLA-G expression in urological tumors as well as its use as a putative biomarker and/or potential therapeutic target for the treatment of renal cell carcinoma as well as urothelial bladder cancer.
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