Tumor‐associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target

Author:

Adawy Ahmad123ORCID,Komohara Yoshihiro14ORCID,Hibi Taizo2

Affiliation:

1. Department of Cell Pathology, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan

2. Department of Pediatric Surgery and Transplantation Kumamoto University Graduate School of Medical Sciences Kumamoto Japan

3. Department of Pediatric Surgery, Faculty of Medicine Mansoura University Mansoura Egypt

4. Center for Metabolic Regulation of Healthy Aging Kumamoto University Kumamoto Japan

Abstract

AbstractThe tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor‐associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM‐derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics. Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage‐mediated antibody‐dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR Mφ) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.

Publisher

Wiley

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