CD47 Expression Is an Independent Prognostic Factor for Recurrence in Resected Non-Small Cell Lung Cancer

Abstract

Background: Immunotherapy is among the most promising advances in oncology. Limited information exists regarding the interrelationship between CD47 expression and the tumour-associated macrophage-related immune microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy. Methods: CD47 and PD-L1 expression was retrospectively studied in 191 resected NSCLC specimens using immunohistochemistry. Additionally, 46 cases with pulmonary infectious diseases were enrolled as a control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated using dual-immunofluorescence staining. Targeted DNA sequencing was performed on all 191 specimens. Finally, the pattern of immune infiltrates was determined and their prognostic role was assessed. Findings: The prevalence of positive CD47 (CD47pos) expression in NSCLC was 33.0% (63/191), significantly higher than that in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking, and adenocarcinoma patients (p=0·020, p<0·001, and p<0·001, respectively). Furthermore, CD47pos expression significantly correlated with EGFR mutation (p<0·001). The expression of CD47 (H-score) in NSCLC negatively correlated with tumour PD-L1 expression (p=0·0334) and tumour mutation burden (p=0·0107). CD47pos expression independently correlated with poor disease-free survival (DFS) for patients with NSCLC in multivariate Cox regression analysis (p=0·035). When CD47 and M2 were combined as combinatorial biomarkers, four patient groups were significantly separated (p<0·001), with negative CD47 expression/absence of M2 in the tumour area showing longer DFS and CD47pos expression/M2 therein exhibiting poor DFS. Interpretation: Our study investigated the demographic, molecular, and immuno-microenvironment characteristics of CD47 expression in NSCLC. We further identified tumour CD47pos expression as an independent prognostic factor for recurrence in NSCLC. Our study illustrates the potential value of anti-CD47 treatment in NSCLC. Funding Statement: This study was supported by the ‘13th Five-Year’ National Science and Technology Major Project for New Drugs (No: 2019ZX09734001-002) by the National Natural Science Foundation of Beijing (to YX) (no. 7194311) and the Fundamental Research Funds for the Central Universities (to YX) (no. 3332018030). This study was funded in part by Innovent Biologics (Suzhou) Co., Ltd. Declaration of Interests: MW received partial research funding from Innovent Biologics (Suzhou) Co., Ltd. and Dizal Pharmaceutical Co., Ltd. The other authors declare no conflicts of interest. Ethics Approval Statement: The study protocol adhered to the World Medical Association Declaration of Helsinki recommendations and was approved by the Ethical Committee of PUMCH (S-K146).