Myeloid Cell Mobilization and Recruitment by Human Mesothelioma in NSG-SGM3 Mice

Abstract

Malignant pleural mesothelioma is a neoplasm that is often detected late due to nonspecific symptoms. This study utilized NSG-SGM3 mice to examine interactions between a human-derived mesothelioma reporter cell line (MZT-Luc2-mCherry) and the host’s myeloid compartment. Tumor growth was assessed using optical tomography, while cytokine/chemokine production was analyzed via multiplex assay. Histological and immunohistochemical analyses validated the epithelioid mesothelioma phenotype. In vitro mesothelioma cells secreted factors associated with myeloid cell chemoattraction and functions supporting the previously reported myeloid-biased secretory phenotype. In line with this, post-engraftment analysis revealed increased neutrophil-like Ly6G+ populations and decreased Ly6C+ inflammatory monocytes in the blood of tumor-bearing mice. Significant Ly6G+ cell infiltration was observed in the tumor, while CD11b+ myeloid cells were localized primarily in the tumor periphery. Tumor lysates showed increased levels of neutrophil chemoattractants and G-CSF, suggesting a previously not reported role of neutrophils in mesothelioma progression. This novel model provides a platform for studying mesothelioma–host interactions, focusing on the myeloid compartment. It may also serve as a tool to facilitate the development of new therapeutic strategies targeting myeloid cell-mediated mechanisms in mesothelioma.

Keywords

• tumor microenvironment
• pro-inflammatory cytokines
• tumor-associated neutrophils
• tumor-associated macrophages