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:Immune reconstitution dynamics after unrelated allogeneic transplantation with post-transplant cyclophosphamide compared to classical immunosuppression with anti-thymocyte globulin: a prospective cohort study.
Immune reconstitution dynamics after unrelated allogeneic transplantation with post-transplant cyclophosphamide compared to classical immunosuppression with anti-thymocyte globulin: a prospective cohort study.
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移植后环磷酰胺(PTCy)促进了单倍体相合造血干细胞移植(HSCT)的成功,也用于匹配供者的移植。然而,关于此类免疫抑制后免疫重建的数据有限。
我们旨在评估无关供者HSCT后的免疫重建,比较抗胸腺细胞球蛋白(ATG)和PTCy。前瞻性纳入连续接受无关供者HSCT并接受ATG或PTCy的患者。通过流式细胞术在移植前及移植后第30、60、90和180天进行免疫重建分析。
我们纳入36例患者,ATG组20例,PTCy组16例。在移植后早期(第[d]+30天),ATG组的总淋巴细胞、T细胞、B细胞和自然杀伤(NK)细胞数量高于PTCy组。
然而,在d+180时,PTCy组的B细胞数量更高。在d+60和d+90时,ATG组的CD56dim NK细胞数量高于PTCy组,而在d+180时,PTCy组的CD56-、CD16+和NKG2D+ NK细胞数量更高。d+60时的初始CD4+、过渡CD4+和初始CD8+ T细胞被确定为急性移植物抗宿主病2-4级的危险因素,d+180时较高的CD4+记忆细胞计数被确定为慢性移植物抗宿主病的危险因素。在无关异基因移植的背景下,与ATG相比,PTCy免疫抑制与更晚的B细胞、T细胞和NK细胞重建相关。
Post-transplant cyclophosphamide (PTCy) has contributed to the success of haploidentical hematopoietic stem cell transplantation (HSCT) and is also used in transplantation from matched donors.
However, limited data on the immune reconstitution after this type of immunosuppression is available.
We aimed to evaluate immune reconstitution after HSCT from unrelated donors, comparing anti-thymocyte globulin (ATG) and PTCy. Consecutive patients undergoing HSCT from unrelated donors and receiving either ATG or PTCy were prospectively included. Immune reconstitution analyses were performed by flow cytometry pre-transplant and on days 30, 60, 90, and 180 post-transplant.
We included 36 patients, 20 in the ATG group and 16 in the PTCy group. In the early post-transplant period (day [d]+30), the ATG group showed a higher number of total lymphocytes, T, B, and natural killer (NK) cells compared to the PTCy group.
However, at d+180, the PTCy group exhibited a higher number of B cells. On d+60 and d+90, the ATG group displayed higher number of NK cells CD56dim compared to the PTCy group, while on d+180, the PTCy group showed higher number of CD56-, CD16+, and, NKG2D+ NK cells.
Naive CD4+, transition CD4+, and naive CD8+ T cells on d+60 were identified as risk factors for acute graft-versus-host disease grade 2-4, and a higher count of CD4+ memory cells on d+180 was identified as a risk factor for chronic graft-versus-host disease. In the context of unrelated allogeneic transplantation, immunosuppression with PTCy was associated with later B-, T- and NK-cell reconstitution compared to ATG.
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