缺乏周细胞覆盖的未成熟脉管系统极大地促进了肿瘤生长、耐药性和癌细胞扩散。我们之前证明肿瘤坏死因子超家族 15 (TNFSF15) 是一种细胞因子，在调节造血和血管稳态中发挥重要作用。本研究的主要目的是探讨TNFSF15是否可以促进新鲜分离的骨髓细胞分化为CD11b细胞并进一步分化为周细胞。在红色荧光骨髓小鼠中建立Lewis肺癌模型。 TNFSF15治疗后，评估肿瘤中的CD11b骨髓细胞和血管周细胞，以及周细胞和血管内皮细胞的共定位。此外，从野生型小鼠中分离出 CD11b 细胞，并用 TNFSF15 进行处理，以确定对这些细胞分化的影响。我们观察到，在 TNFSF15 处理的肿瘤中，骨髓来源的 CD11b 髓样细胞和血管周细胞的百分比升高，而后者细胞与血管内皮细胞共定位。 TNFSF15 通过下调 Wn​​t3a-VEGFR1 和上调 CD49e-FN 信号通路，防止 CD11b 细胞凋亡，并促进这些细胞分化为周细胞。TNFSF15 促进骨髓中 CD11b 细胞的产生并促进这些细胞的分化进入周细胞，这可以稳定肿瘤新血管系统。版权所有 © 2023 Cancer Biology

Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b+ cells and further into pericytes.A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b+ myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b+ cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.We observed elevated percentages of bone marrow-derived CD11b+ myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b+ cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.TNFSF15 facilitates the production of CD11b+ cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.Copyright © 2023 Cancer Biology & Medicine.