CD47-mediated immune evasion in early-stage lung cancer progression

Cheng Hao Chuang, Yen Yi Zhen, Juei Yang Ma, Tai Huang Lee, Huei Yang Hung, Chun Chieh Wu, Pei Hui Wang, Ching Tang Huang, Ming Shyan Huang, Michael Hsiao, Ying Ray Lee, Chi Ying F. Huang, Yu Chan Chang, Chih Jen Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Alveolar and interstitial macrophages play crucial roles in eradicating pathogens and transformed cells in the lungs. The immune checkpoint CD47, found on normal and malignant cells, interacts with the SIRPα ligand on macrophages, inhibiting phagocytosis, antigen presentation, and promoting immune evasion. In this study, we demonstrated that CD47 is not only a transmembrane protein, but that it is also highly concentrated in extracellular vesicles from lung cancer cell lines and patient plasma. Abundant CD47 was observed in the cytoplasm of lung cancer cells, aligning with our finding that it was packed into extracellular vesicles for physiological and pathological functions. In our clinical cohort, extracellular vesicle CD47 was significantly higher in the patients with early-stage lung cancer, emphasizing innate immunity inactivation in early tumor progression. To validate our hypothesis, we established an orthotopic xenograft model mimicking lung cancer development, which showed increased serum soluble CD47 and elevated IL-10/TNF-α ratio, indicating an immune-suppressive tumor microenvironment. CD47 expression led to reduced tumor-infiltrating macrophages during progression, while there was a post-xenograft increase in tumor-associated macrophages. In conclusion, CD47 is pivotal in early lung cancer progression, with soluble CD47 emerging as a key pathological effector.

Original languageEnglish
Article number150066
JournalBiochemical and Biophysical Research Communications
Volume720
DOIs
StatePublished - 6 Aug 2024

Keywords

  • Extracellular vesicles
  • Immune checkpoint
  • Immune evasion
  • Macrophage
  • Tumor microenvironment

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