AI Article Synopsis
- Cancer cells evade destruction by macrophages through CD47, which binds to SIRPα on macrophages; targeting this mechanism is being studied for immunotherapy.
- In a study of 98 non-small cell lung cancers (NSCLCs), high CD68 expression in tumor-associated macrophages correlates with better patient survival, while high SIRPα levels in these macrophages relate to poorer outcomes.
- The findings suggest that the interaction between CD47 on cancer cells and SIRPα on macrophages could be a promising target for improving treatment strategies in operable NSCLC.
Article Abstract
Background: Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRPα ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development.
Methods: We investigated the expression of CD47/SIRPα molecules in a series of 98 NSCLCs, in parallel with the infiltration of tumor stroma by CD68+ macrophages, tumor-infiltrating lymphocytes (TILs), and PD-L1/PD-1 molecules.
Results: Extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed, to a varying extent, by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score in inner tumor areas was linked with improved overall survival ( = 0.005); and this was independent of the stage ( = 0.02, hazard ratio 0.4). In contrast, high SIRPα expression by CD68+ TAMs (SIRPα/CD68-ratio) was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis ( = 0.02). A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs ( = 0.01, r = 0.25) was also noted.
Conclusions: TAMs play an important role in the prognosis of operable NSCLC. As SIRPα+ macrophages adversely affect prognosis, it is suggested that the CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997641 | PMC |
| http://dx.doi.org/10.3390/cancers14071801 | DOI Listing |
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