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 Expression and Its Implications in Non-Small-Cell Lung Cancer Progression and Therapy: A Systematic Review.
TIGIT Expression and Its Implications in Non-Small-Cell Lung Cancer Progression and Therapy: A Systematic Review.
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肺癌(LC)是全球癌症相关死亡的首要原因,非小细胞肺癌(NSCLC)占其中85%–90%。尽管PD-1/PD-L1免疫检查点抑制剂有效,但原发性和获得性耐药凸显了开发新型免疫治疗策略的必要性。研究者依据PICO模型,对2020至2025年的文献进行了系统综述,共纳入6项研究,涵盖I至III期临床试验。分析重点为TIGIT靶向治疗NSCLC的疗效、安全性及新兴治疗策略。阻断TIGIT可增强细胞毒性T淋巴细胞和自然杀伤(NK)细胞活性,从而加强抗肿瘤免疫。临床试验,尤其是单克隆抗体tiragolumab联合PD-1/PD-L1抑制剂的研究,显示出令人鼓舞的协同作用。双特异性抗体(如TIGIT/PD-1和TIGIT/PD-L1抗体)及实验性细胞疗法等新策略也正在研究中,以进一步增强抗肿瘤应答。抗TIGIT疗法是治疗NSCLC的一种很有前景的方法。尽管目前III期数据仍有限,但仍需开展由生物标志物指导且设计完善的试验。若阻断TIGIT的效果得到验证,该策略有望成为NSCLC免疫肿瘤治疗方案的重要组成部分。
Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) representing 85-90% of cases. Despite the efficacy of PD-1/PD-L1 immune checkpoint inhibitors, primary and acquired resistance highlight the need for novel immunotherapeutic strategies. A systematic review of the literature from 2020 to 2025 was conducted according to the PICO model. Six studies were included, encompassing phase I-III clinical trials. The analysis focused on efficacy, safety, and emerging therapeutic strategies targeting TIGIT in NSCLC. TIGIT blockade enhances cytotoxic T lymphocyte and natural killer (NK) cell activity, strengthening antitumor immunity.
Clinical trials, particularly with the monoclonal antibody tiragolumab combined with PD-1/PD-L1 inhibitors, show promising synergistic effects. Emerging strategies, including bispecific antibodies (e. g. , TIGIT/PD-1 and TIGIT/PD-L1) and experimental cell therapies, are under investigation to further improve the antitumor response.
Anti-TIGIT therapies represent a highly promising approach in NSCLC. While phase III data remain limited, biomarker-driven, well-designed trials are essential. If validated, TIGIT blockade could become a key addition to immuno-oncology treatment strategies for NSCLC.
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