Inhibition of Monocyte Recruitment into the Tumor

Creative Biolabs is well equipped and versed in modulating tumor-associated macrophages (TAMs). One approach is to inhibit circulating monocyte recruitment into the tumor. Our professional technical scientists and abundant experience make us a perfect partner to help our clients' projects in this field.

Tumor-derived Factors (TDFs) Involved in Monocyte Recruitment

Tumor promotion by macrophages in different cancer models and increased macrophage prevalence correlates with poor overall survival in many human cancers. This provides a strong basis for targeting macrophages independently at different levels and comparing responses to different targeting strategies. One strategy is to inhibit the recruitment or infiltration of monocytes into tumors. Strong evidence indicates that the accumulation of macrophages in tumors is due to the continuous recruitment of monocytes from the circulation in response to TDFs. These TDFs are key mediators in the crosstalk between monocytes and tumor cells. Several C-C chemokine ligands, such as CCL2, are produced by tumor cells and stroma and they are a major chemoattractant for monocytes, which can then develop into macrophages and promote invasiveness, metastasis and correlate with poor prognosis. CCL2 has been described as the major TDF involved in monocyte recruitment, through the CCL2-C-C chemokine receptor type 2 (CCR2) axis. Another TDF is colony-stimulating factor-1 (CSF-1). CSF1/colony-stimulating factor receptor 1 (CSF1R) signaling orchestrates TAM recruitment and polarization towards a pro-tumor M2 phenotype.

Fig.1 Summary of available therapeutic strategies to target TAMs. (Anfray, 2020)

Strategies for the Inhibition of Monocyte Recruitment at Creative Biolabs

Creative Biolabs combines deep, industry-leading expertise with an innovative Macrophage Therapeutics Development Platform to provide high-quality service in the field of macrophage development. To inhibit circulating monocyte recruitment into the tumor, our seasoned scientists have developed several strategies, including blockade of CCL2-CCR2 axis, CX3CL1/CX3CR1 axis, or CSF1/CSF1-R axis. They are happy to lend their expertise and assist our clients in employing a suitable strategy for their program and help them overcome any hurdles in inhibiting monocyte recruitment.

• CCL2-CCR2 axis
  CCL2–CCR2 axis plays an important role in monocyte recruitment in the tumor in many cancer types. Targeting the CCL2–CCR2 axis is promising as it results in blocking mobilization of monocytes from the bone marrow to the blood, which results in preventing their recruitment to the tumor. CCL2 also promotes a protumor phenotype and its blockade leads to decreased tumor growth and necrosis. Hence, blockade of CCR2 can suppress the accumulation of TAMs in tumors. CCR2 inhibitors and anti-CCL2 antibodies have shown efficacy in reducing tumor growth and metastasis in several pre-clinical murine models.
• CX3CL1/CX3CR1 axis
  Chemokine ligand 1 (CX3CL1) expression in endothelial cells is involved in the CX3CL1 receptor (CX3CR1)-dependent recruitment of immune cells, such as NK cells, CD8+ T cell, and CX3CR1 non-classical monocytes. CX3CL1 expression specifically regulates CX3CR1-expressing monocyte recruitment into tumors without affecting inflammatory monocyte recruitment.
• CSF1/CSF1-R axis
  CSF-1R is known to be essential to the survival of TAM. CSF1/CSF1-R axis drives the recruitment and the differentiation of TAMs toward an M2 phenotype in the tumor. mAbs and small molecules targeting CSF1 or CSF1-R (BLZ945, emactuzumab, PLX3397) have been subjected to numerous studies and were shown to play an important role in monocyte recruitment and to deplete macrophages in a tissue-specific manner.

By assembling top-class scientific experts and integrating state-of-the-art technologies in inhibiting monocyte recruitment, Creative Biolabs has the necessary expertise and capabilities to provide overall solutions, focusing on innovative research. For more information, please feel free to contact us and further discuss with our scientists.

Reference

1. Anfray, C.; et al. Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses. Cells. 2020, 9(1):46.