Heliyon (Jan 2024)

Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma

  • 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

Journal volume & issue
Vol. 10, no. 1
p. e23498

Abstract

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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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