Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma

PD-1 的表达减轻了骨肉瘤中 TAM 的吞噬活性

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作者:Chenhong Zheng, Heng Li, Xiaohui Zhao, Siyu Yang, Jinqin Zhan, Huaie Liu, Yan Jiang, Li Shi, Yaxian Song, Yujie Lei, Tingdong Yu, Xiaoxiong Wang, Hongsheng Li, Xi Wang, Yushan Xu, Zhihong Yao

Abstract

The high expression of programmed death 1 (PD-1) is a hallmark of T cell exhaustion, consequently inhibiting the anti-tumor immunity, tumor-associated macrophages (TAMs) aggravate Osteosarcoma (OS) progression. However, PD-1 expression on TAMs in OS metastasis remains unclear. Here, we used scRNA-Seq of 15500 individual cells from human OS lung metastatic lesion, identified thirteen major cell clusters. Our data revealed that tumor-infiltrating lymphocytes (TILs) OS lung metastatic accompanied by accumulation of exhausted T cells and regulatory T cells (Tregs). CD3+ T cells from human OS lung metastatic exhibited lower proliferation than in primary tissue. Importantly, TAMs mainly comprise immunosuppressive M2 phenotype in OS metastasis. Mechanistically, we found that PD-1 of TAMs inhibits the phagocytic potency, further promoting the progression of OS metastasis. Therefore, the study provides a strong technical support for OS immunotherapy based on PD-1 inhibitors.

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