The Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp2) is generally considered to be an oncogene owing to its ability in enhancing the malignancy of multiple types of tumor cells; however, its role in modulating tumor immunity remains largely elusive. Here, we reported that myeloid-restricted ablation of Shp2 suppressed melanoma growth. Mechanistically, loss of Shp2 potentiates macrophage production of CXCL9 in response to IFN-γ and tumor cell-derived cytokines, thereby facilitating the tumor infiltration of IFN-γ-producing T cells that could in turn support CXCL9 production within tumor microenvironment. Collectively, our findings highlight a causative role of myeloid Shp2 in dampening T cell-mediated antitumor immunity by restraining the macrophage/CXCL9-T cell/IFN-γ feedback loop. Thus, targeting macrophage Shp2 may help to create a Th1-dominant tumor immune microenvironment.

中文翻译：

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Shp2的髓样限制消融通过放大肿瘤微环境中CXCL9和IFN-γ产生的相互促进来抑制黑素瘤的生长。

含有Src同源性2结构域的蛋白酪氨酸磷酸酶2（Shp2）由于具有增强多种类型肿瘤细胞恶性性的能力而被普遍认为是致癌基因。然而，其在调节肿瘤免疫力中的作用仍然难以捉摸。在这里，我们报道了Shp2的髓样限制消融抑制了黑色素瘤的生长。从机制上讲，Shp2的丧失增强了对IFN-γ和肿瘤细胞衍生的细胞因子的巨噬细胞CXCL9的产生，从而促进了肿瘤向IFN-γ产生的T细胞的浸润，从而又支持了肿瘤微环境中CXCL9的产生。总的来说，我们的发现突出了髓样蛋白Shp2通过抑制巨噬细胞/ CXCL9-T细胞/IFN-γ反馈回路而减弱T细胞介导的抗肿瘤免疫力的原因。因此，