The role of CD47 in immune escape of colon cancer and its correlation with heterogeneity of tumor immune microenvironment.

Abstract

Background: Cluster of differentiation 47 (CD47), a transmembrane protein, plays a critical role in regulating cellular functions and maintaining immune homeostasis. Its expression has been shown to influence cancer prognosis. In this study, we investigated the role of CD47 in tumor progression in colon adenocarcinoma (COAD) and evaluated its potential as a target for immunotherapy.

Materials and methods: We analyzed surgical samples from 96 COAD patients. Immunohistochemical analysis was performed on 90 samples, while the remaining 6 were subjected to multiplex immunofluorescence. To explore the association between CD47 expression and clinicopathological characteristics, we integrated transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus using R software. The Tumor Immune Estimation Resource and Kaplan-Meier plotter were utilized to assess the relationship between CD47 expression, patient prognosis, and immune infiltration. Furthermore, the single-cell Tumor Immune System Interaction Database was used to examine the correlation between CD47 expression and the tumor microenvironment (TME). All included patients gave oral and written informed consent. The study was approved by the Ethics Committee of 3201 Hospital (full name: Medical Ethics Committee of 3201 Hospital).

Results: CD47 was found to be overexpressed in various tumors, including COAD. Higher CD47 expression was significantly associated with more advanced tumor stages, including TNM staging, T staging, and N staging (P < 0.05). A robust correlation was observed between CD47 expression and immune cell infiltration in COAD. Patients with elevated CD47 expression tended to have longer disease-free intervals, although this benefit was diminished in cases with high infiltration of M1 macrophages. The immunosuppressive function of CD47 primarily acted through the CD47/SIRPα pathway. Additionally, distinct cellular compositions and distributions were identified between primary and metastatic COAD, underscoring the heterogeneity of the TME. CD47 also influenced the TME by modulating cytokine and cytokine receptor interactions.

Conclusion: CD47 represents a promising prognostic biomarker and a potential target for immunotherapy in COAD. These findings provide new insights into therapeutic strategies aimed at modulating the TME and improving patient outcomes.