Macrophages, being critical components of the immune system, have a highly dynamic and versatile nature. In the context of liver cancer, they exhibit diverse polarization states that greatly influence the tumor's biology. The polarization of macrophages toward pro-tumoral (M2-like) or anti-tumoral (M1-like) states can drastically affect tumor progression and the efficacy of treatments.

We explore the critical role of macrophages in liver cancer, with a focus on how macrophage polarization influences tumor dynamics and the immune response. Creative Biolabs will showcase the comprehensive services, which are designed to support and accelerate research on macrophages in liver cancer and the development of targeted therapeutic strategies.

The Role of Macrophages in Liver Cancer

Macrophages are versatile immune cells that reside in various tissues, including the liver, where they serve multiple functions such as immune defense, tissue repair, and homeostasis. In the context of liver cancer, macrophages exist predominantly in two polarization states: M1 macrophages (anti-tumoral) and M2 macrophages (pro-tumoral).

Fig.1 Macrophages origin and heterogeneity.^1,3

• TAMs promote cancer cell proliferation, invasion, and metastasis

M2 macrophages have been shown to play an essential role in promoting cancer cell migration in HCC via the TLR4/STAT3 signaling pathway. Aberrant activation of the NTS/IL-8 pathway plays a pro-tumorigenic role in the inflammatory microenvironment of HCC. IL-6 derived by macrophages can induce epithelial-mesenchymal transition (EMT) of HCC cells, and promote HCC invasion and metastasis. Moreover, CXCL8 produced by activated macrophages increases the expression of miR-17 cluster in HCC cells and promotes HCC progression and metastasis.

• TAMs promote angiogenesis and cancer cell stemness

TAMs have been demonstrated to produce a variety of angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and several matrix metalloproteinases (MMPs). The high heterogeneity and malignancy of liver cancer are partly attributed to cancer stem cells (CSCs), which promote tumor recurrence, metastasis, and development of resistance to therapies. TAMs have been suggested to promote CSC-like properties via various signaling pathways, such as TGF-β signaling pathway and Wnt/β-catenin signaling pathway.

• TAMs promote autophagy

Mounting evidence suggests the importance of autophagy in the regulation of the function of TAMs and antitumor immunity [91]. Studies have shown that autophagy-deficient Kupffer cells promoted liver fibrosis, inflammation, and hepatocarcinogenesis. Moreover, baicalin can inhibit live cancer development and progression by repolarizing TAM towards the M1 phenotype via autophagy-associated activation of RelB/p52.

• TAMs modulate therapeutic resistance

The orally administrated multikinase inhibitor sorafenib shows limited efficacy in HCC patients due to the development of intolerance and resistance. TAM has been demonstrated to induce immunosuppression and weaken the efficacy of sorafenib in HCC [97]. Moreover, oxaliplatin-based chemotherapies are widely used in patients with advanced HCC. It has been reported that TAMs are important drivers of resistance to oxaliplatin by trigging autophagy and apoptosis evasion in HCC cells. The density of TAMs in HCC samples has been associated with the efficiency of transarterial chemoembolization in HCC.

Fig.2 Therapeutic strategies targeting TAMs in HCC.^2,3

Creative Biolabs Services for Studying Macrophages in Liver Cancer

At Creative Biolabs, we offer specialized macrophage polarization assays to study the complex dynamics of macrophage activation and polarization in liver cancer. Our assays are designed to enable detailed analysis of macrophage polarization and their functional characteristics, allowing researchers to understand how these cells interact with liver cancer cells and influence tumor progression.

Macrophage Polarization Assays for Liver Cancer Research

• M1/M2 Macrophage Polarization Assay: This assay enables researchers to induce M1 or M2 polarization in macrophages in vitro. By using specific cytokines and inhibitors, we can control the polarization process and measure key markers such as surface receptors (e.g., CD80 for M1, CD163 for M2), cytokine secretion profiles, and gene expression changes.
• Macrophage-Conditioned Medium (MCM) Analysis: Macrophage-conditioned medium is a valuable tool to study the paracrine signaling in liver cancer. Our service enables the collection of secreted factors from polarized macrophages (both M1 and M2) and their impact on liver cancer cells. The medium is analyzed for key cytokines (e.g., IL-6, IL-10, TGF-β) that mediate immune suppression or anti-tumor activity.
• TAM Profiling in Liver Cancer Tissues: Our TAM profiling service allows for the extraction and characterization of TAMs from liver cancer tissue samples. We assess the polarization status of TAMs and their functional attributes using flow cytometry and immunohistochemistry.
• Macrophage Tumor Cell Co-Culture Assay: In liver cancer research, studying the interaction between macrophages and tumor cells in a co-culture system provides valuable information about tumor progression. We offer customized co-culture models where macrophages (polarized toward M1 or M2) are cultured with liver cancer cells (e.g., HCC cell lines).

Cytokine and Chemokine Profiling in Liver Cancer

Macrophages secrete a wide array of cytokines and chemokines that significantly influence tumor progression. The secretion profiles of these immune mediators are key to understanding the inflammatory environment of liver cancer. At Creative Biolabs, we offer specialized cytokine and chemokine profiling services to monitor the immune response in liver cancer models.

• Multiplex Cytokine Assay: Using state-of-the-art multiplex assays, we provide a comprehensive profile of key cytokines involved in macrophage polarization. These assays can measure multiple cytokines simultaneously, such as TNF-α, IL-6, IL-10, IL-12, TGF-β, and others.
• Chemokine Profiling: Our chemokine profiling services allow for the detection and quantification of chemokines secreted by liver cancer cells and macrophages.
• Inflammatory Cytokine Blocking Assay: To explore the effects of cytokine inhibition, we offer assays that block specific cytokines involved in macrophage polarization. For example, blocking IL-4 and IL-13 can prevent M2 polarization, while targeting IFN-γ can affect M1 activation.

Why Choose Creative Biolabs?

• Liver-Centric Expertise: Our team understands the unique physiology of the liver, including the fenestrated endothelium and the role of hepatic stellate cells in modulating macrophages.
• Customization: Every project is tailored. Whether you need a specific cytokine profile or a custom-engineered cell line, we deliver.
• Data Integrity: We provide comprehensive reports with raw data, high-resolution imaging, and statistical analysis ready for publication or regulatory filing.
• Global Reach: Serving top pharmaceutical companies and academic institutions worldwide with rapid turnaround times.

Macrophage-targeting Therapies in Liver Cancer

Increasing evidence suggests the critical roles of TAMs in the development and progression of liver cancer. Hence, immunotherapies targeting TAMs have emerged as a promising approach to treat patients with liver cancer. The current therapeutic strategies targeting TAMs include phagocytosis-promoting therapies, inhibition of monocyte recruitment, elimination of pre-existing TAMs in the tumor tissue, reprogramming TAM polarization, and neutralizing pro-tumorigenic factors secreted by TAMs.

Table 1 Agents targeting TAMs for the treatment of liver cancer. (Huang, 2021)

Creative Biolabs' Macrophage Research Solutions

At Creative Biolabs, we offer a comprehensive suite of macrophage-related services to support liver cancer research. Our services are designed to accelerate your research by providing:

Related Products

Creative Biolabs stands out as a trusted partner for liver cancer research and macrophage-related studies and provides extensive range of reagent products for your macrophage workflows. For Research Use Only.

Scientific Resources

Q & A

Q: How will Creative Biolabs' macrophage polarization assays advance my research?

A: Our macrophage polarization assays are designed to give you precise control over the macrophage phenotype in liver cancer models. By using specific cytokines and inhibitors, we can reliably induce and assess the polarization of macrophages into either M1 or M2 phenotypes. These assays help you measure the secretion profiles of cytokines, assess immune cell function, and evaluate how macrophages interact with liver cancer cells.

Q: Can your services distinguish between resident Kupffer Cells (KCs) and recruited Monocyte-Derived Macrophages (Mo-Macs) in HCC models?

A: Yes, this distinction is critical because these two populations have distinct roles in the HCC TME. Our immunophenotyping panels are specifically designed for this purpose. We can provide comparative functional analysis (e.g., cytokine secretion profiles or phagocytic capacity) for both subsets to help you understand which population is the primary driver of your therapeutic target's effect.

Q: We are developing a "Don't Eat Me" signal inhibitor. How do you validate the pro-phagocytic effect in a liver-specific context?

A: Our phagocytosis assay platform is highly specialized for HCC. We label liver cancer cell lines with pH-sensitive fluorescent dyes or CFSE. These labeled tumor cells are then co-cultured with M1 or M2 polarized macrophages in the presence of your drug candidate. We provide live-cell imaging, flow cytometry quantitation and efferocytosis analysis.

Q: What is the typical turnaround time for a macrophage polarization and drug-screening project?

A: The timelines vary based on complexity. This includes cell isolation, characterization, polarization induction, drug treatment, and data analysis. We provide progress reports to keep you updated on every milestone.

For more detailed information or to discuss how we can assist with your macrophage-targeted liver cancer research, please contact us. Our team is here to provide expert guidance and support to help you achieve your research goals.

Reference

1. Tian, Zhiqiang, et al. "Macrophages and hepatocellular carcinoma." Cell & bioscience 9.1 (2019): 79. https://doi.org/10.1186/s13578-019-0342-7
2. Huang, Yu, et al. "The role of tumor associated macrophages in hepatocellular carcinoma." Journal of Cancer 12.5 (2021): 1284. https://doi.org/10.7150/jca.51346
3. Distributed under Open Access license CC BY 4.0, without modification.