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:A Killer Disarmed: Natural Killer Cell Impairment in Myelodysplastic Syndrome.
A Killer Disarmed: Natural Killer Cell Impairment in Myelodysplastic Syndrome.
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由于骨髓增生异常综合征(MDS)具有异质性且可能进展为急性髓系白血病(AML),其治疗仍是重大挑战。唯一可能治愈疾病的方法是异基因造血干细胞移植(HSCT),但大多数患者不适合接受该手术,只能选择姑息治疗,因此该疾病领域存在显著未满足需求。自然杀伤(NK)细胞能够无需预先致敏即可靶向髓系白血病细胞,因此是MDS免疫治疗的理想候选细胞。近年来,AML以及近期MDS领域的临床试验数量不断增加。据报道,MDS患者的NK细胞功能严重异常,但可通过NK细胞过继免疫治疗或激活内源性NK细胞予以克服。本文综述NK细胞在MDS中的作用、肿瘤微环境(TME)对NK细胞功能受损的影响,以及MDS领域基于NK细胞的临床试验最新数据。
Myelodysplastic syndrome (MDS) treatment remains a big challenge due to the heterogeneous nature of the disease and its ability to progress to acute myeloid leukemia (AML). The only curative option is allogeneic hematopoietic stem cell transplantation (HSCT), but most patients are unfit for this procedure and are left with only palliative treatment options, causing a big unmet need in the context of this disease.
Natural killer (NK) cells are attractive candidates for MDS immunotherapy due to their ability to target myeloid leukemic cells without prior sensitization, and in recent years we have seen an arising number of clinical trials in AML and, recently, MDS. NK cells are reported to be highly dysfunctional in MDS patients, which can be overcome by adoptive NK cell immunotherapy or activation of endogenous NK cells.
Here, we review the role of NK cells in MDS, the contribution of the tumor microenvironment (TME) to NK cell impairment, and the most recent data from NK cell-based clinical trials in MDS.
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