The prognosis of cancers is closely related to the number of tumor-associated macrophages (TAMs) with an inverse correlation. An increased number of TAMs is associated with reduced survival. TAMs are generally polarized into either of two extremes, classical activated M1 subtype and alternatively activated M2 subtype. TAMs usually express an M2-like phenotype and participate in tumor angiogenesis, tumor invasion, tumor metastasis, and immunosuppression. Reprogramming TAMs toward M1-like macrophages would thus be an efficient way to promote tumor regression. Integrating state-of-the-art Macrophage Therapeutics Development Platform as well as industry-leading expertise in TAM reprogramming, Creative Biolabs is committed to providing overall solutions, focusing on innovative research. Our scientists are fully competent and dedicated to helping our clients' research and project development.

Background of TAM Reprogramming

Plasticity and diversity allow their classification along an M1-M2 polarization axis. TAMs can be educated by the tumor microenvironment they experience, providing multiple phenotypes with a broad range of functions. The polarization of macrophages can be driven by different microenvironmental molecules and leads to the production by the macrophages of different cytokines and chemokines. M1 macrophages are activated during acute inflammation by toll-like receptor (TLR) ligands or T helper type 1 (Th1) cytokines. M1 macrophages display an enhanced production of pro-inflammatory cytokines, such as TNFα and interleukins (ILs): IL-1β, IL-2, IL-6, IL-12, IL-23. While stimulation of macrophages with IL-4/IL-13, IL-10, transforming growth factor-β (TGFβ), or glucocorticoids leads to the M2 phenotype. M2 macrophages express cell surface scavenger receptor (CD206), hemoglobin receptor (CD163) and produce extracellular matrix (ECM) components. They decrease inflammation, encourage tissue repair, and provide pro-tumoral effects. They also favor tumor growth. TAMs usually exhibit an M2 phenotype and thus promote tumor progression, metastasis, and resistance to therapy. Therefore, there is a key interest to create strategies for reprogramming TAMs from M2-like to an M1-like phenotype and thereby induce immune effects that can bring about tumor regression.

Fig.1 Macrophage polarization.^1,2

Tumor-associated Macrophage (TAM) Reprogramming Service at Creative Biolabs

• Reprogramming TAMs with Nanomedicine

Nanomedicine represents a versatile platform that exploits nanoparticles, which are fine-tuned nanoscale materials for drug delivery and diagnosis. Various functionalized nanomedicines have been designed to repolarize TAM from pro-tumorigenic M2-like to tumoricidal M1-like macrophages. Creative Biolabs has developed several efficient strategies to reprogram TAMs to M1 phenotype with nanomedicines.

• Reprogramming TAMs by Targeting Signaling Pathway

There are several mechanisms involved in macrophage polarization, includinginterferon-regulatory factor/signal transducer and activator of transcription (IRF/STAT) signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and Janus kinase (JAK)/STAT signaling, which provides an intriguing opportunity to reprogramming tumor-promoting M2-like TAMs toward tumoricidal M1 phenotype. Creative Biolabs has perfected our technical pipelines in reprogramming TAMs to M1 phenotype by targeting signaling pathways.

• Reprogramming TAMs with Anticancer Therapies

Targeting the reprogramming of TAMs toward M1-like macrophages can be achieved through therapies including chemotherapy (chemical compounds) or immunotherapy, such as Toll-like receptors (TLRs), stimulator of interferon genes (STING) agonists and monoclonal antibody (mAbs), targeting macrophage reprogramming could also synergize their effects on tumor regression. By leveraging the wealth of information that we have on anticancer therapies for TAM reprogramming, we provide our clients with highly customizable solutions.

• Reprogramming TAMs by Monoclonal Antibodies (mAbs)

M2 macrophages may be repolarized to M1 macrophages by altering specific cytokines in a tumor. This can be implemented by mAbs, such as anti-CSF1R mAbs, anti-CCL2 mAbs, anti-CD47 mAbs or anit-signal regulatory protein alpha (SIRPα) signaling mAbs. Creative Biolabs is committed to providing overall solutions for TAM reprogramming by mAbs, focusing on innovative research.

Creative Biolabs offers turn-key or ala carte services customized to our client's needs. Please contact us for more information and a detailed quote.

References

1. Genard, Géraldine, Stéphane Lucas, and Carine Michiels. "Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo-and immunotherapies." Frontiers in immunology 8 (2017): 828.
2. Under Open Access license CC BY 4.0, without modification.