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:TIGIT, a novel immune checkpoint therapy for melanoma.
TIGIT, a novel immune checkpoint therapy for melanoma.
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黑色素瘤是侵袭性最强、最致命的皮肤癌类型。在过去10年中,包括PD-1/PD-L1和CTLA-4抑制剂在内的免疫检查点阻断(ICB)已被证明对黑色素瘤有效。PD-1/PD-L1和CTLA-4抑制剂在黑色素瘤患者治疗中显示出不同程度的耐药性。此外,ICB的临床获益还伴随严重的免疫毒性。因此,迫切需要开发新的免疫检查点抑制剂,以优化黑色素瘤治疗并降低细胞毒性。具有免疫球蛋白和免疫受体酪氨酸抑制基序结构域的T细胞免疫受体(TIGIT)被认为可激活T细胞、自然杀伤(NK)细胞和调节性T细胞(Tregs)中的抑制性受体,并已成为一种有前景的免疫治疗靶点。研究发现,TIGIT可在黑色素瘤不同阶段被检测到,这与黑色素瘤的发生、发展和预后密切相关。本综述主要阐述TIGIT的免疫抑制机制及其在黑色素瘤抗肿瘤免疫中的作用,从而为靶向TIGIT的黑色素瘤临床治疗提供新思路和方案。
Melanoma is the most aggressive and deadliest type of skin cancer. In the last 10 years, immune checkpoint blockades (ICBs) including PD-1/PD-L1 and CTLA-4 inhibitor has been shown to be effective against melanoma. PD-1/PD-L1 and CTLA-4 inhibitors have shown varying degrees of drug resistance in the treatment of melanoma patients.
Furthermore, the clinical benefits of ICBs are also accompanied by severe immune toxicity.
Therefore, there is an urgent need to develop new immune checkpoint inhibitors to optimize melanoma therapy and reduce cytotoxicity. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is thought to activate inhibitory receptors in T cells, natural killer (NK) cells, and regulatory T cells (Tregs), and has become a promising target for immunotherapy.
Studies have found that TIGIT can be detected in different stages of melanoma, which is closely related to the occurrence, development, and prognosis of melanoma. This review mainly describes the immunosuppressive mechanism of TIGIT and its role in antitumor immunity of melanoma, so as to provide new ideas and schemes for the clinical treatment of melanoma with targeted TIGIT.
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