High expression of B7-H3 on monocyte/macrophages in tumor microenvironment promotes lung cancer progression by inhibiting apoptosis

  • Transl Oncol. 2024 Jan 22:41:101874. doi: 10.1016/j.tranon.2023.101874.
Dongze Zhang  1 ,  Haitao Huang  2 ,  Xin Gao  3 ,  Gehua Yu  3 ,  Xueguang Zhang  1 ,  Haiyan Jin  1 ,  Ruyan Xu  1 ,  Zhenxin Wang  4 ,  Guangbo Zhang  5
Affiliations
  • 1. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, China.
  • 2. Department of Thoracic surgery, The First Affiliated Hospital of Soochow University, China.
  • 3. Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, China.
  • 4. Department of Medical Oncology, The First Affiliated Hospital of Soochow University, China. Electronic address: [email protected].
  • 5. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, China. Electronic address: [email protected].
PMID: 38262113 DOI: 10.1016/j.tranon.2023.101874
Abstract

Monocyte/macrophages constitute a significant population of tumor-infiltrating immune cells and play a crucial role in tumor growth, invasion, and metastasis. B7-H3, has immune regulatory functions, however, it is unclear whether B7-H3 expressed on monocyte/macrophages plays a significance role in tumor progression. We found B7-H3 was high-expressed on monocyte/macrophages in tumor microenvironment compared with adjacent tissues in lung Cancer, and its expression level was positively correlated with the number of monocyte/macrophages. Furthermore, the expression of B7-H3 was related to clinical stage and lymph node metastasis. Moreover, miR-29a-3p negatively regulated B7-H3, and the expression of B7-H3 on THP-1-derived macrophages was regulated by secreting exosomes containing miR-29a-3p. In addition, knockdown of B7-H3 promoted macrophage Apoptosis under hypoxia. Mechanistically, B7-H3 enhanced the antiapoptotic ability of macrophage by up-regulating HIF-1ɑ via activating NF-κB. Taken together, these results imply that B7-H3 as a therapeutic target could hold promise for enhancing anti-tumor immune responses in individuals diagnosed with lung Cancer.

Keywords
B7-H3; Exosome; HIF-1ɑ; Lung cancer; Monocyte/macrophages.
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