PD-1的表达减轻了骨肉瘤中肿瘤相关巨噬细胞的吞噬活性。
Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma.
作者信息
Zheng Chenhong, Li Heng, Zhao Xiaohui, Yang Siyu, Zhan Jinqin, Liu Huaie, Jiang Yan, Shi Li, Song Yaxian, Lei Yujie, Yu Tingdong, Wang Xiaoxiong, Li Hongsheng, Wang Xi, Xu Yushan, Yao Zhihong
机构信息
Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China.
Department of Thoracic Surgery I&II, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan, 650118, China.
出版信息
Heliyon. 2023 Dec 13;10(1):e23498. doi: 10.1016/j.heliyon.2023.e23498. eCollection 2024 Jan 15.
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.
程序性死亡蛋白1(PD-1)的高表达是T细胞耗竭的标志,从而抑制抗肿瘤免疫,肿瘤相关巨噬细胞(TAM)会加剧骨肉瘤(OS)的进展。然而,OS转移中TAM上PD-1的表达仍不清楚。在此,我们对来自人类OS肺转移灶的15500个单个细胞进行了单细胞RNA测序(scRNA-Seq),鉴定出13个主要细胞簇。我们的数据显示,肿瘤浸润淋巴细胞(TIL)在OS肺转移时伴随着耗竭T细胞和调节性T细胞(Treg)的积累。来自人类OS肺转移灶的CD3 T细胞的增殖低于原发组织。重要的是,在OS转移中TAM主要包含免疫抑制性M2表型。从机制上讲,我们发现TAM的PD-1抑制吞噬能力,进一步促进OS转移的进展。因此,该研究为基于PD-1抑制剂的OS免疫治疗提供了有力的技术支持。