University of Florida, College of Medicine, Division of Hematology-Oncology, Gainesville, Florida, USA.
Cytotherapy. 2011 Aug;13(7):888-96. doi: 10.3109/14653249.2011.579956. Epub 2011 May 24.
Granulocyte-macrophage (GM) colony-stimulating factor (CSF) has been used as an adjuvant in cancer immunotherapy. We tested the hypothesis that GM-CSF (Leukine(®); sargramostim) improves immune reconstitution after hematopoietic stem cell transplantation (HSCT) based on our prior in vitro work that demonstrated the pro-inflammatory effects of GM-CSF on dendritic cells (DC).
GM-CSF was administered to donors, along with standard granulocyte (G) CSF, during stem cell mobilization, and to recipients from the day prior to transplant until engraftment. Eighteen patients consented to the GM-CSF(+) protocol and were compared with 17 matched controls undergoing HSCT during the same time period (GM-CSF(-)).
Numbers of white blood cells (WBC) and CD34(+) stem cells in the graft were comparable to controls. Surprisingly, contrary to our hypothesis, the allogeneic donor graft had significantly decreased numbers of CD3(+) T cells and their subsets (CD4(+), CD4(+) CD45RA(+), CD4(+) CD45RO(+), CD8(+) and CD8(+) CD45RO(+)), DC (both myeloid and plasmacytoid) and natural killer (NK) cells (CD16(+) CD56(+)). In the GM-CSF arm, following allogeneic transplantation, the levels of DC, T cells and NK cells did not increase with treatment. Conversely, autologous transplant patients receiving GM-CSF had a higher proportion of DC at the time of engraftment.
These findings demonstrate that administration of GM-CSF improves DC reconstitution after autologous rather than allogeneic HSCT.
粒细胞-巨噬细胞集落刺激因子(GM-CSF)已被用作癌症免疫治疗的佐剂。我们基于之前的体外研究结果(GM-CSF 对树突状细胞(DC)具有促炎作用),假设 GM-CSF(Leukine®;沙格司亭)可改善造血干细胞移植(HSCT)后的免疫重建。
在干细胞动员期间,GM-CSF 与标准粒细胞(G)CSF 一起给予供者,并且在移植前一天到植入时给予接受者。18 名患者同意接受 GM-CSF(+)方案,并与同期接受 HSCT 的 17 名匹配对照(GM-CSF(-))进行比较。
移植物中的白细胞(WBC)和 CD34+干细胞数量与对照组相当。出人意料的是,与我们的假设相反,同种异体供体移植物中 CD3+T 细胞及其亚群(CD4+、CD4+CD45RA+、CD4+CD45RO+、CD8+和 CD8+CD45RO+)、DC(髓样和浆细胞样)和自然杀伤(NK)细胞(CD16+CD56+)的数量显著减少。在 GM-CSF 组中,在同种异体移植后,DC、T 细胞和 NK 细胞的水平并未随治疗而增加。相反,接受 GM-CSF 的自体移植患者在植入时具有更高比例的 DC。
这些发现表明,GM-CSF 的给药可改善自体而不是异体 HSCT 后的 DC 重建。