我们报告了一种细胞群体的鉴定，它具有血管周细胞、基质和干性特征，不携带KrasG12D突变，并在体内外驱动肿瘤生长。我们将这些细胞称为血管周干细胞（PeSCs），并将它们定义为CD45- EPCAM- CD29+ CD106+ CD24+ CD44+细胞。我们进行了p48-Cre; KrasG12D(KC)、pdx1-Cre;KrasG12D;Ink4a/Arffl/fl (KIC) 以及pdx1-Cre;KrasG12D;p53R172H(KPC)和PDAC和慢性胰腺炎患者的肿瘤组织的研究。我们还进行了单细胞RNA测序分析，并揭示了PeSC的独特标志。在稳态条件下，PeSC在胰腺中几乎不可检测，但存在于人类和小鼠的肿瘤微环境中。PeSC和肿瘤上皮细胞的共同注射导致肿瘤生长增强、Ly6G+髓源性抑制细胞的分化增强、F4/80+巨噬细胞和CD11c+树突状细胞的数量减少。当与上皮肿瘤细胞共同注射时，这种细胞群体会引起抗PD-1免疫治疗的耐药性。我们的数据揭示了一种细胞群体的存在，它指导免疫抑制性髓细胞的反应，以绕过PD-1的靶向作用，因此可能提出克服临床免疫治疗的耐药性的潜在新方法。 ©2023作者。在CC BY NC ND 4.0许可证条款下发表。

We report the identification of a cell population that shares pericyte, stromal and stemness features, does not harbor the KrasG12D mutation and drives tumoral growth in vitro and in vivo. We term these cells pericyte stem cells (PeSCs) and define them as CD45- EPCAM- CD29+ CD106+ CD24+ CD44+ cells. We perform studies with p48-Cre;KrasG12D (KC), pdx1-Cre;KrasG12D ;Ink4a/Arffl/fl (KIC) and pdx1-Cre;KrasG12D ;p53R172H (KPC) and tumor tissues from PDAC and chronic pancreatitis patients. We also perform single-cell RNAseq analysis and reveal a unique signature of PeSC. Under steady-state conditions, PeSCs are barely detectable in the pancreas but present in the neoplastic microenvironment both in humans and mice. The coinjection of PeSCs and tumor epithelial cells leads to increased tumor growth, differentiation of Ly6G+ myeloid-derived suppressor cells, and a decreased amount of F4/80+ macrophages and CD11c+ dendritic cells. This population induces resistance to anti-PD-1 immunotherapy when coinjected with epithelial tumor cells. Our data reveal the existence of a cell population that instructs immunosuppressive myeloid cell responses to bypass PD-1 targeting and thus suggest potential new approaches for overcoming resistance to immunotherapy in clinical settings.© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.