Although the precise composition of the tumor microenvironment (TME) varies in an organ-dependent manner, tumor-associated macrophages (TAMs) have emerged as one of the most numerous and critical cell types, with potent multifaceted roles in regulating cancer progression and modulating the response to therapeutic intervention. By decreasing the permissive nature of the tumor microenvironment, macrophage depletion may allow the host's defenses to recover and eliminate tumor cells. By assembling top-class scientific experts and integrating a state-of-the-art Macrophage Therapeutics Development Platform as well as industry-leading expertise in the depletion of TAM, Creative Biolabs offers accurate and effective solutions for our clients who need help in TAM depletion. Our seasoned scientists will work together closely to address these scientific and technical challenges.

Background of Depletion of TAMs

Tumors develop and progress within a complex tissue environment involving a multitude of intercellular interactions, not only between heterogeneous cancer cells but also with the many normal cell types that collectively comprise the TME. TAMs are a major leukocyte subset in many cancers and are capable of potently suppressing endogenous or treatment-induced antitumor T-cell responses. They are the most abundant immune cells in the TME and are known to have an M2-like pro-metastatic phenotype, which directly supports migration, adhesion and invasion of tumor cells. Infiltration of TAM is linked to angiogenesis, and tumor aggressiveness. Accordingly, these M2-like TAMs are promising targets for inhibiting cancer. However, previous researches have indicated that targeting TAMs from the tumor microenvironment synergized the effect of immunotherapy therapies, suggesting that TAMs are major causes of immunotherapy resistance. Depletion of this immune-suppressive cell type may render previously immune resistant or escaped tumors sensitive to checkpoint inhibition, chemo- and radiotherapy, and cellular therapies. Therefore, TAM depletion could potentially reactivate antitumor immunity. Studies have indicated that TAM depletion combined with an effective dendritic cell (DC)-mediated antitumor T-cell response is capable of producing durable tumor responses and functional antitumor immunity.

FFig.1 Macrophage depletion is a potential target between TAMs and CD8-positive (CD8+) T cells.^1,2

TAM Depletion Service at Creative Biolabs

With an experienced team of in-house TAM depletion experts, Creative Biolabs employs efficient strategies, including depletion of TAMs by colony-stimulating factor 1 receptor (CSF1R) blockade and specific depletion of TAMs by mAbs, to provide our clients with highly customizable solutions. From project design to in-depth analysis, our seasoned scientists will work with our clients to develop a complete solution for their development needs.

• Depletion of TAMs by CSF-1R blockade

The growth factor CSF-1 is involved in the proliferation, differentiation, and survival of monocytes/macrophages that originated from bone marrow progenitor cells. A high level of CSF-1 or CSF-1R expression in the tumor or peri-tumor tissue has been associated with poor patient survival in several types of cancers. Strong evidence supports the CSF-1/CSF-1R axis as an attractive target to reduce the number of TAMs in tumors.

• Specific depletion of TAMs by mAbs

Using mAbs (such as mAbs targeting CD163) conjugated with lipid nanoparticles (NPs) loaded with doxorubicin has shown selective depletion of CD163+ macrophages and re-education of TME through increased recruitment of T cells and monocytes, which both contribute to tumor regression.

By leveraging the wealth of information that we have on TME depletion, Creative Biolabs is pleased to share our cutting-edge technology and extensive expertise in TAM depletion to facilitate our clients' research and project development. For more information, please feel free to contact us and further discuss with our scientists.

References

1. Tu, Sheng, et al. "Crosstalk between tumor-associated microglia/macrophages and CD8-positive T cells plays a key role in glioblastoma." Frontiers in Immunology 12 (2021): 650105.
2. Under Open Access license CC BY 4.0, without modification.