Clinicopathological significance of CD47 expression in hepatocellular carcinoma

Abstract

AimsCD47 is upregulated on the surface of various tumour cells, and it is known to inhibit the phagocytosis of tumour cells by macrophages. Immunotherapy that targets CD47 has demonstrated success in preclinical trials and is now under clinical investigation for both solid and haematological malignancies. However, data regarding CD47 expression in hepatocellular carcinoma (HCC) tissue and its correlation with clinical outcomes in patients with HCC remain limited. Here, we investigated the clinicopathological features associated with CD47 expression in HCC.MethodsCD47 expression was evaluated by immunohistochemistry in tissue microarray sections containing 166 HCC tissues. CD47 expression was considered positive if 10% or more tumour cells were stained.ResultsCD47 expression was observed in 36 (21.7%) of 166 HCC tissues and was significantly associated with frequent large vessel invasion, advanced American Joint Committee on Cancer stage and higher Ki-67 proliferation index. In the survival analyses, CD47 expression was not associated with recurrence-free survival or overall survival in total patients with HCC. However, in patients who received surgical resection without any adjuvant treatment, CD47 expression was associated with shorter recurrence-free survival.ConclusionsCD47 expression was significantly associated with adverse pathological features and poor clinical outcomes in patients with HCC who did not receive adjuvant treatment.

Comprehensive Analysis of the Correlation Between Pyroptosis-Related LncRNAs and Tumor Microenvironment, Prognosis, and Immune Infiltration in Hepatocellular Carcinoma

“…Several clinical trials on CD47-targeting agents are ongoing that have shown promising results ( Chester et al, 2015 ; Liu et al, 2015 ). Kim et al demonstrated that CD47 is upregulated in HCC tumor tissues and correlated with shorter recurrence-free survival ( Kim et al, 2021 ). The differences in PD-1 and CD47 expression between the clusters and normal and tumor samples were also analyzed.…”

Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer

“…Adopting a similar behavior, cancer cells overexpress CD47 to escape M1 macrophage innate immune response by binding to their SIRPα ligand. Increased expression of CD47 has been documented in hematological malignancies and also in various human solid tumors [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Restoring the innate macrophage immunity by targeting the CD47/SIRPα axis is under intense preclinical and clinical evaluation [ 3 , 4 ].…”

“…The expression patterns of CD47 in human malignancies have been investigated in a small number of published studies, mainly from Eastern Institutes. Association with aggressive clinical behavior and poor prognosis have been reported in breast [ 5 ], esophageal [ 6 ] and gastric cancer [ 7 ], as well as hepatomas [ 8 ], and melanomas [ 9 ]. In non-small cell lung cancer (NSCLC), contradictory results have been published in four reports [ 10 , 11 , 12 , 13 ].…”

Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future

“…Binding of CD47 to its receptor signal regulatory protein a (SIRPa) on macrophages inhibits phagocytosis activation and can contribute to tumor formation [113,114]. CD47 is therefore overexpressed on various hematologic and solid tumors to evade the cellular immune response, including HCC where it is also associated to poorer outcome [21]. Consequently, blocking CD47-signaling inhibited growth of HCC models and restored sensitivity to chemotherapy [115].…”

“…In the context of human cancer therapy, the currently most studied ICIs are PD1 (programmed cell death protein 1), CTLA-4 (cytotoxic T lymphocyte protein 4), LAG-3 (lymphocyte activation gene 3 protein), and, TIM-3 (T cell immunoglobulin and mucin-domain containing)-for an overview including the respective ligands, see also Figure 2. [16][17][18][19][20][21][22]. Abbreviations: APC, antigen-presenting cell;…”