Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma

Sun, Haoyu; Song, Jiuzhou; Weng, Chenchun; Xu, Jing; Huang, Mei; Huang, Qiang; Sun, Rui; Xiao, Weihua; Sun, Cheng

doi:10.1111/jgh.13633

Cited by 29 publications

(25 citation statements)

References 24 publications

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“…The literature to date on the prognostic significance of MARCO in cancer is sparse. Sun et al (22) reported that a decreased expression of MARCO was associated with tumor progression and poor prognosis in hepatocellular carcinoma and Lundgren et al (23) showed that high density of MARCO + TAMs in certain subtypes of periampullary pancreatic cancer predicted shorter survival. To the best of our knowledge, the expression and prognostic impact of MARCO in GE adenocarcinoma has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

et al. 2020

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Background: Despite improvements in surgical methodologies and perioperative chemo-and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68 + , CD163 + , and MARCO + macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan-Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68 + and CD163 + , but not MARCO + , macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68 + TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163 + TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68 + macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02-2.55, and p = 0.041). Conclusion: Infiltration of CD68 + and CD163 + , but not MARCO + , macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

et al. 2020

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“…A similar mechanism of action, promoting the anti-tumoral functions of macrophages in tumors, has been observed for anti-MARCO mAbs, in murine models of breast, colon cancer, and melanoma [ 145 ]. These antibodies target the pattern-recognition scavenger receptor, MARCO, which is overexpressed in TAMs and linked to poor prognosis in breast, lung, and hepatic cancer [ 146 , 147 , 148 ]. Bispecific antibodies, targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), showed TAMs reprogramming and delayed tumor growth in glioma murine models [ 149 ].…”

Section: Monoclonal Antibodies To Reprogram Tamsmentioning

confidence: 99%

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Belgiovine

Digifico

Anfray

et al. 2020

JCM

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In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.

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“…For example, Kupffer cells can be divided into two types, namely CD68+MARCO- (macrophage receptor with collagen structure) and CD68+MARCO+cells ( MacParland et al 2018 ). The up-regulation of Marco expression inhibits the migration and invasion of HCC cells, thereby alleviating tumor progress ( Sun et al, 2017 ). Furthermore, the massive infiltration of CD68+CD163+ macrophages and total CD68+ macrophages are related to the poor prognosis of HCC patients, while CD68+CD169+ macrophages and CD68+CD38+ macrophages are the opposite ( Lam et al, 2019 ; Li et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

Chen

Zheng

et al. 2020

PeerJ

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Background Macrophage play a crucial role in regulating tumor progression. This study intended to investigate the circular RNA (circRNA) regulatory network associated with macrophage infiltration in hepatocellular carcinoma (HCC). Methods The immune cell fractions of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium were calculated by Estimation of the Proportion of Immune and Cancer cells algorithm. The differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) were identified from HCC and adjacent non-tumor cases of TCGA or Gene Expression Omnibus database. The DEmRNAs related to macrophage were selected by weighted gene co-expression network analysis and then utilized to generate the circRNA-miRNA-mRNA network. A hub circRNA regulatory network was established based on the co-expressed DEmiRNAs and DEmRNAs owning contrary correlation with the clinical characteristics, survival and macrophage infiltration level. A gene signature based on the DEmRNAs in hub network was also generated for further evaluation. The circRNA binding bite for miRNA was detected by luciferase assay. Results High macrophage fraction predicted good survival for HCC. A circRNA-miRNA-mRNA network was constructed by 27 macrophage related DEmRNAs, 21 DEmiRNAs, and 15 DEcircRNAs. Among this network, the expression of hsa-miR-139-5p was negatively correlated with CDCA8, KPNA2, PRC1 or TOP2A. Hsa-miR-139-5p low or targeted DEmRNA high expression was associated with low macrophage infiltration, high grade, advanced stage and poor prognosis of HCC. Additionally, the risk score generated by 4-DEmRNA signature could reflect the macrophage infiltration status and function as an independent prognostic factor for HCC. Finally, hsa_circ_0007456 acting on hsa-miR-139-5p related network was viewed as the hub circRNA regulatory network. Taken together, some circRNA regulatory networks may be associated with macrophage infiltration, which provides clues for mechanism study and therapeutic strategies of HCC.

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Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma

Abstract: Our study is the first to demonstrate an association between MARCO expression and the progression and prognosis of HCC.

Cited by 29 publications

References 24 publications

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

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