Patrolling monocytes inhibit osteosarcoma metastasis to the lung

Abstract

Immune infiltration is associated with osteosarcoma metastasis. However, previous studies have not accounted for the functional diversity of the cells involved in the immune response. We conducted a comprehensive comparative analysis of the tumor-infiltrating immune cells in metastatic and non-metastatic osteosarcoma tissues based on a deconvolution algorithm (CIBERSORT). Twenty-two immune cell subsets were evaluated for their association with the presence or absence of metastasis in osteosarcoma patients. A lack of monocytes was associated with osteosarcoma metastasis; however, the levels of M1 macrophages, M2 macrophages and other immune cell subsets did not differ between the metastatic and non-metastatic groups. Additionally, a higher proportion of monocytes was associated with a better prognosis in osteosarcoma patients. Animal experiments demonstrated that the number of metastatic nodules was higher in mice lacking patrolling monocytes than in control mice. Our data indicated that the cellular composition of the immune infiltrate may subtly differ among osteosarcoma patients, and that patrolling monocytes inhibit osteosarcoma metastasis to the lungs of mice. Thus, the composition of the immune infiltrate and the level of patrolling monocytes may be important determinants of whether metastasis occurs in osteosarcoma patients.