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Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma

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机构: [1]Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China [2]Bone and Soft Tissue Tumors Research Centre of Yunnan Province, Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan, 650118, China [3]Department of Cancer Center Office, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, 650118, China [4]Department of Thoracic Surgery I&II, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan, 650118, China [5]Department of Ultrasound, Hohhot First Hospital, Hohhot City, 010059, Inner Mongolia Autonomous Region, China [6]Ultrasonic Department, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China [7]Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China [8]Molecular Diagnostic Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China [9]Department of Endocrinology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China
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关键词: Osteosarcoma PD-1 Tumor-associated macrophages Metastasis scRNA-seq

摘要:
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.

基金:

基金编号: 82160125 81960488 2021J0263 2023Y0654 2019EF001 [-236] 2023SYY (BS) 019 202101AY070001- [171] NCC201925B02 2023535D14 H-2019072 202001AY070001-195 149 150 202201AY070001-168 170 136 041 160 CXTD202106 2020J0197 2022J0235

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China
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通讯机构: [2]Bone and Soft Tissue Tumors Research Centre of Yunnan Province, Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan, 650118, China [3]Department of Cancer Center Office, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, 650118, China [*1]Bone and Soft Tissue Tumors Research Centre of Yunnan Province, Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan, 650118, China
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