肿瘤微环境（TME）中的髓系细胞可以存在免疫抑制和免疫刺激状态，分别阻碍或促进抗肿瘤免疫。阻断抑制性髓系细胞或增加刺激性细胞以增强抗肿瘤免疫应答是治疗干预的一个感兴趣领域。髓系细胞表达的激发细胞受体1（TREM1）是一种促炎受体，可放大免疫应答。TREM1表达在中性粒细胞、单核细胞亚群和组织巨噬细胞上，并且存在于TME中具有抑制作用的髓系细胞群体中，包括肿瘤相关中性粒细胞、单核细胞和肿瘤相关巨噬细胞。清除或抑制免疫抑制性髓系细胞或通过TREM1介导的炎性信号刺激，可以用于促进免疫刺激性TME。我们开发了PY159，一种缺糜蛋白化的人源化髓系细胞受体1单克隆抗体，其FcγR结合能力得到增强。PY159是一种TREM1激动剂，可诱导信号传导，在体外可促使单核细胞和巨噬细胞上共刺激分子的上调，产生促炎性细胞因子和趋化因子，并增强T细胞活化。针对小鼠TREM1的抗体，PY159m，在同基因小鼠肿瘤模型中促进抗肿瘤疗效。这些结果表明，在肿瘤髓系细胞上通过PY159来激动TREM1可能会促使炎症性TME，为免疫治疗提供了有前景的策略。

Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor immune responses is an area of interest for therapeutic intervention. Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the TME, including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Depletion or inhibition of immunosuppressive myeloid cells, or stimulation by TREM1-mediated inflammatory signaling, could be used to promote an immunostimulatory TME. We developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody with enhanced FcγR binding. PY159 is a TREM1 agonist that induces signaling, leading to up-regulation of costimulatory molecules on monocytes and macrophages, production of proinflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy.