Macrophages play critical roles in the regulation of homeostasis, inflammation, and antitumor immunity in a tissue-specific and context-dependent manner. These cells are commonly classified into classically activated (M1) macrophages and alternatively activated (M2) macrophages. M2 macrophages are able to impair antitumor immunity, which in turn contributes to the immunosuppressive tumor niche. Blockade of the key factors involved in M2 macrophage polarization is an efficient way to inhibit M2 polarization. Experienced in the research of macrophage polarization and with a dedicated commitment to the scientific community, Creative Biolabs has developed several strategies for the blockade of M2 macrophage. Our multidisciplinary scientists will work together closely to address these scientific and technical challenges.

Factors Involved in M2 Macrophage Polarization

In tumors, infiltrating macrophages, also known as tumor-associated macrophages (TAMs), present an M2 state, exerting an inhibitory effect on the cytotoxic function of tumor-killing immune cells M2 macrophage polarization involves tyrosine phosphorylation and activation of a signal transducer and activator of transcription (STAT)6. STAT3 and STAT6 are two main transcription factors that have been largely reported to block M2 polarization. STAT3 phosphorylation on tyrosine is mainly regulated by members of Janus-activated kinases (JAK), while its phosphorylation on serine is commonly regulated by mitogen-activated protein kinases. STAT6 mediates the transcriptional activation of a range of M2-specific genes, including arginase 1, resistin-like α, mannose receptor 1, chitinase-like protein 3, and the chemokine genes CCL17 and CCL24. The essential positive role of STAT6 in macrophage M2 polarization is reflected by the enhanced expression of M2 genes in STAT6-overexpressing macrophages, whereas the ablation of STAT6 abolishes M2 gene expression.

Strategies for the Blockade of M2 Macrophage at Creative Biolabs

By assembling top-class scientific experts and integrating a cutting-edge Macrophage Therapeutics Development Platform as well as industry-leading expertise in the research of macrophage polarization, Creative Biolabs is committed to providing comprehensive services in the blockade of M2 macrophage. Our scientists have perfected our technical pipelines for the blockade of M2 macrophage using tyrosine kinase inhibitors, STAT3 inhibitors or STAT6 inhibitors.

• Using tyrosine kinase inhibitors to block M2 phenotype
  Sunitinib is a small-molecule multitargeted receptor tyrosine kinase inhibitor. Sunitinib and sorafenib are two tyrosine kinase inhibitors that inhibit STAT3 in macrophages. Sunitinib inhibits STAT3 activity in macrophages, leading to reduced expression of several STAT3-regulated angiogenic genes, while sorafenib can restore the secretion of IL-12 while suppressing IL-10 expression in prostaglandin E2-conditioned macrophages, indicating a reverse effect on the immunosuppressive cytokine profile in TAMs.
• Using STAT3 inhibitors to block M2 phenotype
  WP1066 is designed to target the STAT3 pathway in tumor cells. WP1066 inactivates STAT3 and suppresses the growth and viability of renal cancer cells. Treatment with WP1066 stimulated the secretion of pro-inflammatory cytokines and activated T cells. While, resveratrol, possessing two phenol rings linked to each other by an ethylene bridge, is a stilbenoid polyphenol produced by several plants in response to injury. Studies have shown that resveratrol promoted the M2 polarization of microglia and reduced neuroinflammation in the injured brain. The blockade of M2-like polarization of TAMs by resveratrol was linked to the decreased activity of STAT3.
• Using STAT6 inhibitors to block M2 phenotype
  Fenretinide is a synthetic retinoid derivative and inhibits the growth of several human cancer cell lines. Fenretinide can inhibit the phosphorylation of STAT6 and skew M2 polarization. The effects were accompanied by a reduction in the number of M2-like macrophages in the tumor of a colorectal mouse model.

Creative Biolabs is pleased to share our knowledge in the blockade of M2 macrophage to facilitate our clients' research and project development. We offer turn-key or ala carte services customized to our client's needs. Please contact us for more information.