Potential contribution of tumor-associated slan+ cells as anti-CSF-1R targets in human carcinoma

Abstract

The precise identification of the types and respective roles of the tumor-associated myeloid cells, which include tumor-associated Mϕs (TAMs), neutrophils, dendritic cells, and myeloid-derived suppressor cells, is under intensive investigation. Although tumor-associated myeloid cells may contribute to tumor cell eradication by virtue of their effector functions, they are retained to fulfill predominantly protumorigenic roles. It follows that depletion of tumor-associated myeloid cells represents one of the currently pursued therapeutic options in advanced malignancies. In that regard, RG7155/emactuzumab, a specific anti-CSF-1R humanized Ab, has been reported recently to deplete CSF-1R⁺ TAMs, in association with objective clinical responses in patients with advanced cancer. Because RG7155/emactuzumab has also been shown to deplete blood non-classic CD14^dim/- CD16⁺⁺ monocytes, which in large part include the CD16⁺⁺ slan⁺ monocytes, we asked whether RG7155/emactuzumab could target tumor-associated slan⁺ cells. In this study, we confirmed that slan⁺ cells localize only to metastatic tumor-draining lymph nodes, not to primary tumors or distant metastases in patients with different types of carcinoma. Notably, by cell scoring on serial sections, we found that slan⁺ cells represent a minor fraction of the total CSF-1R⁺ cell pool, suggesting that slan⁺ cells potentially represent minor targets of anti-CSF-1R therapy. Therefore, a protumorigenic role for slan⁺ cells, such as that of CSF-1R⁺ TAMs, based on our current data, remains questionable.

Keywords: non-classic CD14dim/−CD16++ monocyte; tumor-associated Mϕ; tumor-draining lymph node.