Marco, known as macrophage receptor with collagenous structure, is a member of scavenger receptor class A (SR-A) [2]. It shares structural and functional similarities with SR-A1, triggers immune responses, and is crucial in bridging innate and adaptive immunity, as well as eliminating pathogens [2]. It can sequester pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, suppressing immune responses [3]. Marco is also involved in pathways like TNF/NFκB signaling, KRAS signaling, PI3K/AKT/mTOR pathway, IL-6-STAT3 signaling, TGFβ pathway, and p53 pathway [1].

In gene-related functional studies, Marco-deficient conditions lead to exacerbated liver inflammation in animal models. Intestinal barrier leakage-induced inflammation in periportal zones is markedly augmented in Marco-deficient conditions, and functional ablation of Marco + macrophages leads to primary sclerosing cholangitis (PSC)-like inflammatory phenotypes related to colitis and exacerbates steatosis in non-alcoholic steatohepatitis (NASH) [3]. In porcine alveolar macrophages (PAMs), knockdown of Marco enhances porcine reproductive and respiratory syndrome virus (PRRSV) proliferation, while overexpression suppresses it. This shows that Marco serves as a host restriction factor for PRRSV through regulating apoptosis [4]. Blocking Marco + tumor-associated macrophages (TAMs) in liver cancer can improve anti-PD-L1 therapy. Marco + TAMs suppress IFN-β secretion, reducing antigen presentation molecule expression, infiltration, and causing CD8 + T cell dysfunction. The combination of Marco and PD-L1 monoclonal antibodies can significantly inhibit liver cancer growth [5].

In conclusion, Marco plays essential roles in immune regulation, anti-viral defense, and cancer-related immune evasion. Studies using gene knockout or conditional knockout mouse models have revealed its significance in liver-related inflammatory diseases, anti-viral responses, and cancer immunotherapy. These findings contribute to understanding the biological functions of Marco and provide potential therapeutic targets for relevant diseases [3,4,5].

References:

1. Dong, Qingyu, Zhang, Shunhao, Zhang, Haotian, Wang, Guihua, Wang, Xudong. 2023. MARCO is a potential prognostic and immunotherapy biomarker. In International immunopharmacology, 116, 109783. doi:10.1016/j.intimp.2023.109783. https://pubmed.ncbi.nlm.nih.gov/36773567/

2. Zhou, Guiyuan, Zhang, Lei, Shao, Suxia. 2024. The application of MARCO for immune regulation and treatment. In Molecular biology reports, 51, 246. doi:10.1007/s11033-023-09201-x. https://pubmed.ncbi.nlm.nih.gov/38300385/

3. Miyamoto, Yu, Kikuta, Junichi, Matsui, Takahiro, Takeda, Kiyoshi, Ishii, Masaru. 2024. Periportal macrophages protect against commensal-driven liver inflammation. In Nature, 629, 901-909. doi:10.1038/s41586-024-07372-6. https://pubmed.ncbi.nlm.nih.gov/38658756/

4. Zhang, Xiaoxiao, Chen, Yongjie, Li, Songbei, Liu, Xiaohong, Guo, Chunhe. 2023. MARCO Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection through Intensifying Viral GP5-Induced Apoptosis. In Microbiology spectrum, 11, e0475322. doi:10.1128/spectrum.04753-22. https://pubmed.ncbi.nlm.nih.gov/37078873/

5. Ding, Limin, Qian, Junjie, Yu, Xizhi, Zhou, Lin, Zheng, ShuSen. 2023. Blocking MARCO+ tumor-associated macrophages improves anti-PD-L1 therapy of hepatocellular carcinoma by promoting the activation of STING-IFN type I pathway. In Cancer letters, 582, 216568. doi:10.1016/j.canlet.2023.216568. https://pubmed.ncbi.nlm.nih.gov/38065400/