Enhanced Expression of CD47 Is Associated With Off-Target Resistance to Tyrosine Kinase Inhibitor Gefitinib in NSCLC

Nigro, Annunziata; Ricciardi, Luca; Salvato, Ilaria; Sabbatino, Francesco; Vitale, Monica; Crescenzi, Maria Assunta; Montico, Barbara; Triggiani, Massimo; Pepe, Stefano; Stellato, Cristiana; Casolaro, Vincenzo; Col, Jessica Dal

doi:10.3389/fimmu.2019.03135

Cited by 49 publications

(47 citation statements)

References 50 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kaur et al 28 showed that anti-CD47 (B6H12) treatment decreases EGFR expression and inhibits EGF-induced EGFR tyrosine phosphorylation in breast cancer stem cells. Nigro et al 29 found that CD47 expression became up-regulated following in vitro drug resistance development, and blocking this protein by a specific monoclonal antibody increased the clearance of EGFR tyrosine kinase inhibitor (TKI)-resistant cells by phagocytes. We hypothesise that CD47/SIRPα axis inhibition is a potential antitumour immunotherapy strategy for EGFR mutant NSCLC with acquired resistance to EGFR-TKI.…”

Section: Discussionmentioning

confidence: 99%

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

Tong

et al. 2020

ESMO Open

View full text Add to dashboard Cite

BackgroundImmunotherapy 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 methodsCD47 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.ResultsUsing 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than 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 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). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).ConclusionThis study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

Tong

et al. 2020

ESMO Open

View full text Add to dashboard Cite

show abstract

“…CD47 interacts with signal regulatory protein alpha (SIRPα), inhibiting phagocytosis by macrophages and DCs. The blockade of CD47 with a monoclonal antibody allows for phagocytosis of dying cells [81] also in the absence of CRT exposure [82]. However, the role of CD47 in ICD has yet to be fully elucidated.…”

Section: Crtmentioning

confidence: 99%

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

et al. 2020

Self Cite

View full text Add to dashboard Cite

The safety and feasibility of dendritic cell (DC)-based immunotherapies in cancer management have been well documented after more than twenty-five years of experimentation, and, by now, undeniably accepted. On the other hand, it is equally evident that DC-based vaccination as monotherapy did not achieve the clinical benefits that were predicted in a number of promising preclinical studies. The current availability of several immune modulatory and targeting approaches opens the way to many potential therapeutic combinations. In particular, the evidence that the immune-related effects that are elicited by immunogenic cell death (ICD)-inducing therapies are strictly associated with DC engagement and activation strongly support the combination of ICD-inducing and DC-based immunotherapies. In this review, we examine the data in recent studies employing tumor cells, killed through ICD induction, in the formulation of anticancer DC-based vaccines. In addition, we discuss the opportunity to combine pharmacologic or physical therapeutic approaches that can promote ICD in vivo with in situ DC vaccination.

show abstract

“…There are a lot of data suggesting that the innate immune response plays a fundamental role in modulating tumor phagocytosis through the CD47-SIRP α axis. CD47 was first identified as a tumor antigen on human ovarian cancer in the 1980s; since then, CD47 has been found to be overexpressed on multiple hematologic and nonhematologic malignancies, including chronic myeloid leukemia (CML), non-Hodgkin's lymphoma (NHL) [ 15 ], multiple myeloma [ 16 ], breast cancer [ 17 ], pancreatic cancer [ 18 ], nonsmall cell lung cancer (NSCLC) [ 19 , 20 ], and other solid tumors. Increased expression of CD47 on tumors allows malignant cells to escape innate immune surveillance through evasion of phagocytosis by interacting with SIRP α on myeloid cells.…”

Section: The Role Of Cd47 In Cancer Pathophysiologymentioning

confidence: 99%

“…Recently, an in vitro study presented by Nigro et al demonstrated that CD47 expression became upregulated in EGFR mutated NSCLC cell lines following the development of resistance to Gefitinib and blocking of CD47 by a specific mAb increased the clearance of EGFR -TKI resistant cells by phagocytes. Furthermore, on TKI-sensitive cell lines, EGFR inhibition significantly reduced CD47 expression on the surface of preapoptotic cells, favoring more efficient engulfment of cancer cells by monocyte-derived dendritic cells [ 20 ]. The results of these studies are on line with those recently reported by our group, which demonstrated that the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS [ 42 ].…”

Section: Cd47- Sirp α In Nonsmall Cell Lung Canmentioning

confidence: 99%

CD47-SIRPαAxis as a Biomarker and Therapeutic Target in Cancer: Current Perspectives and Future Challenges in Nonsmall Cell Lung Cancer

Catalán

Orozco‐Morales

Hernández‐Pedro

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

CD47 is a cell surface protein in the immunoglobulin superfamily which is normally expressed at low levels in every healthy cell. It´s main physiologic function is to act as an inhibitor of phagocytosis; this occurs throughout interaction with SIRPa expressed on macrophages. Interaction between CD47 and SIRPa leads to activation of tyrosine phosphatases that inhibit myosin accumulation at the submembrane assembly site of the phagocytic synapse, resulting in phagocytosis blockade. In this way CD47 acts as a “don´t eat me signal” for healthy self-cells; accordingly, loss of CD47 leads to phagocytosis of aged or damaged cells. Taking advantage of this anti-phagocytic signal provided by CD47, many types of tumors overexpress this protein, thereby avoiding phagocytosis by macrophages and aiding in the survival of cancer cells. The aim of this review is to describe the physiologic the pathophysiologic role of CD47; summarize the available high-quality information about this molecule as a potential biomarker and/or therapeutic target in cancer; finally, we present an in-depth analysis of the available information about CD47 in association with nonsmall cell lung cancer, EGFR mutations, and tumor microenvironment.

show abstract

Enhanced Expression of CD47 Is Associated With Off-Target Resistance to Tyrosine Kinase Inhibitor Gefitinib in NSCLC

Cited by 49 publications

References 50 publications

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

CD47-SIRPαAxis as a Biomarker and Therapeutic Target in Cancer: Current Perspectives and Future Challenges in Nonsmall Cell Lung Cancer

Contact Info

Product

Resources

About