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:Targeting TIGIT for cancer immunotherapy: recent advances and future directions.
Targeting TIGIT for cancer immunotherapy: recent advances and future directions.
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作为一种新发现的检查点,T细胞免疫受体与免疫球蛋白和酪氨酸抑制基序(ITIM)结构域(TIGIT)在CD4 + T细胞、CD8 + T细胞、自然杀伤(NK)细胞、调节性T细胞(Tregs)和TIL(肿瘤浸润淋巴细胞)(TILs)上高表达。TIGIT已在体内及多种癌症患者中与NK细胞耗竭相关。它不仅调节NK细胞存活,还介导T细胞耗竭。作为人类TIGIT的主要配体,CD155因其与TIGIT的相互作用可能成为免疫治疗的主要靶点。已发现癌症免疫治疗中抗程序性细胞死亡蛋白1(PD-1)治疗反应与CD155相关,但与TIGIT无关。抗TIGIT单药及与抗PD-1药物联合已用于癌症免疫治疗试验。尽管两项关于晚期肺癌的临床研究取得了积极结果,但靶向TIGIT的抗体tiragolumab最近在两项新试验中失败。在这篇综述中,我们重点介绍TIGIT在癌症免疫治疗中的当前进展,并讨论TIGIT的特征和功能。
As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4 + T cells, CD8 + T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT.
It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.
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