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.
肿瘤细胞治疗研究
英文原题:Advances in cellular therapies for children and young adults with solid tumors.
Advances in cellular therapies for children and young adults with solid tumors.
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综述目的:过继性免疫疗法为确诊高危实体瘤的儿童和青年带来希望。嵌合抗原受体(CAR)T细胞、CAR自然杀伤(NK)细胞及T细胞受体(TCR)T细胞等细胞疗法,是具有潜力的靶向治疗途径,长期毒性有限。然而,实体瘤细胞疗法的发展仍处于起步阶段。本文回顾当前临床经验、疗效障碍,以及提升临床应答和患者可及性的策略。 近期发现:研究显示,细胞疗法总体安全且耐受性良好。优化抗肿瘤活性的策略已进入早期临床试验。免疫抑制性肿瘤微环境仍是疗效的主要障碍,目前研究正致力于加深对它的认识,为制定增强细胞疗法抗肿瘤活性的未来策略提供依据。 总结:迄今的临床经验为如何利用细胞疗法治疗实体瘤提供了重要见解。推动该领域发展的关键因素包括更深入理解免疫细胞生物学、肿瘤细胞行为及肿瘤微环境。此外,在临床试验实施和未来纳入标准治疗时,提高患者获得新型细胞疗法的机会仍十分重要。
PURPOSE OF REVIEW: Adoptive immunotherapy brings hope to children and young adults diagnosed with high-risk solid tumors. Cellular (cell) therapies such as chimeric antigen receptor (CAR) T cell, CAR natural killer (NK) cell, and T cell receptor (TCR) T cell therapy are potential avenues of targeted therapy with limited long-term toxicities.
However, development of cell therapies for solid tumors is in its nascent stages.
Here, we will review the current clinical experience, barriers to efficacy, and strategies to improve clinical response and patient access. RECENT FINDINGS: Cell therapies are shown to be generally safe and well tolerated. Strategies to optimize antitumor activity have now moved into early-phase trials. The immunosuppressive tumor microenvironment remains a major barrier to efficacy, and efforts are underway to gain better understanding.
This will inform future treatment strategies to enhance the antitumor activity of cell therapies. SUMMARY: Clinical experiences to date provide important insights on how to leverage cell therapies against solid tumors. Key factors in advancing the field include a better understanding of immune cell biology, tumor cell behavior, and the tumor microenvironment. Lastly, improving access to novel cell therapies remains an important consideration in the conduct of clinical trials and for future implementation into standard practice.
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