The effect of beta-glucan - induced trained immunity on the transcriptomic profile of bone marrow granulocyte-macrophage progenitors (GMP) in tumor-bearing mice

Induction of trained immunity by beta-glucan has been shown to promote transcriptomic alterations in myeloid cells. Progenitors in the bone marrow are also affected by trained immunity and also regulate anti-tumor immune responses . In this study, we performed RNA sequencing in GMP from tumor-bearing mice in order to investigate the impact of trained immunity on the transcriptomic profile of myeloid progenitors in the tumor setting. WT mice were pretreated with a single dose of 1 mg of β-glucan from Trametes versicolor (Invivogen) in PBS or with PBS vehicle alone (control) and were then injected subcutaneously with 3 x 105 B16-F10 melanoma cells into the right flank. Bone marrow GMP (Lin—c-Kit+Sca1—CD16/32+CD34+) were sorted 14 days after tumor cell injection and RNA sequencing analysis was performed.

研究证实，β-葡聚糖介导的训练免疫（trained immunity）可诱导髓系细胞发生转录组层面的改变。骨髓中的髓系祖细胞不仅会受到训练免疫的调控，同时也参与调节抗肿瘤免疫应答。本研究以荷瘤小鼠的粒细胞-巨噬细胞祖细胞（granulocyte-macrophage progenitors, GMP）为研究对象开展RNA测序，旨在探究训练免疫对肿瘤微环境中髓系祖细胞转录组特征的影响。实验分组如下：野生型（WT）小鼠预先接受单剂量1mg云芝（Trametes versicolor）来源β-葡聚糖（由Invivogen公司提供，溶于磷酸盐缓冲液（PBS）中）处理，对照组小鼠仅注射等量PBS溶剂；随后于两组小鼠右侧背部皮下接种3×10^5个B16-F10黑色素瘤细胞。接种肿瘤细胞14天后，分选小鼠骨髓GMP（细胞表型为Lin—c-Kit+Sca1—CD16/32+CD34+）并进行RNA测序分析。