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:Immunotherapy for myelodysplastic syndrome and acute myeloid leukemia: where do we stand?
Immunotherapy for myelodysplastic syndrome and acute myeloid leukemia: where do we stand?
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探索检查点抑制剂用于 MDS 和 AML 的初期临床试验已显示出高毒性和令人失望的疗效。
引言:骨髓增生异常综合征(MDS)和急性髓系白血病(AML)总体预后较差,现有治疗效果有限。免疫疗法已成功用于多种恶性肿瘤,其在髓系肿瘤管理中的作用也在迅速发展。综述范围:本文综述已在MDS和AML中测试的免疫疗法,包括免疫检查点抑制剂、双特异性抗体,以及嵌合抗原受体(CAR)T细胞、T细胞受体(TCR)工程化T细胞和自然杀伤(NK)细胞等细胞疗法,重点讨论迄今开展的临床试验和未来方向。专家观点:最初探索MDS和AML免疫检查点抑制剂的临床试验毒性较高、疗效令人失望。然而,将新型检查点抑制剂加入标准治疗的在研试验更有希望。技术进步改善了双特异性抗体的发展前景;早期试验中,过继NK细胞输注等细胞疗法显示出较好的疗效和耐受性。随着对MDS和AML免疫微环境的认识不断加深,免疫疗法在这些疾病治疗中的作用将会更加清楚。
INTRODUCTION: Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are generally characterized by a poor prognosis with currently available therapies. Immunotherapies have already seen success in treating a variety of malignant disorders, and their role in managing myeloid cancers is evolving rapidly.
AREAS COVERED: This is a review of the immunotherapies tested in MDS and AML, including immune checkpoint inhibitors, bispecific antibodies, and cell therapies such as chimeric antigen receptor (CAR) T cell therapy, T cell receptor (TCR) engineered T cells, and natural killer (NK) cells, with a focus on clinical trials conducted to date and future directions. EXPERT OPINION: Initial clinical trials exploring checkpoint inhibitors in MDS and AML have demonstrated high toxicity and disappointing efficacy.
However, ongoing trials adding novel checkpoint inhibitors to standard therapy are more promising. Technological advances are improving the outlook for bispecific antibodies, and cellular therapies like adoptive NK cell infusion have favorable efficacy and tolerability in early trials. As our understanding of the immune microenvironment in MDS and AML improves, the role for immunotherapy in the treatment of these diseases will become clearer.
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