ESMO Open · 2020 · 32 citations · 35 references
MedicineImmunologyOncologyCancer ImmunologyImmunotherapyTumor MicroenvironmentCancer ImmunotherapyImmuno-oncology BiomarkersLung CancerTumor Immune MicroenvironmentTumor-associated MacrophagesTumor-infiltrating LymphocytesCd8+ Tumor-infiltrating LymphocytesImmunofluorescence StainingLung AdenocarcinomaLung Cancer PathologyNon-small Cell Lung Cancer ImmunotherapyNon-small Cell Lung Cancer TherapyPrognostic BiomarkersTumor Microenvironment Biomarkers
Background Immunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy. Patients and methods CD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model. Results Using 2+/3+ as a CD47 positive (CD47 pos ) expression cut-off, the prevalence of CD47 pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47 pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47 pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47 pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035). Conclusion This study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47 pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.
35
Rebecca L. Siegel, Kimberly D. Miller, Ahmedin Jemal · CA A Cancer Journal for Clinicians · 2020 · 21.4K citations · Full text
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Martin Reck, Delvys Rodríguez‐Abreu, Andrew Robinson et al. · New England Journal of Medicine · 2016 · 10.1K citations · Full text
Medicine, Oncology, Pharmacology +17
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
H. Borghaei, L. Paz-Ares, Leora Horn et al. · New England Journal of Medicine · 2015 · 9.5K citations · Full text
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Julie R. Brahmer, Karen L. Reckamp, Lucio Crinò et al. · New England Journal of Medicine · 2015 · 8.6K citations · Full text
Pharmacy, Oncology, Pharmacotherapy +15
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Paul C. Tumeh, Christina L. Harview, Jennifer H. Yearley et al. · Nature · 2014 · 6.6K citations · Full text
Life Sciences, Immunology, Pathology +14