(P 65) INVESTIGATING MACROPHAGE POPULATIONS IN PRIMARY AND METASTATIC SARCOMA SAMPLES

Objective: Sarcomas display high metastatic potential to the lung. Studies in other malignancies emphasize the tumor microenvironment in metastasis. Macrophages are important in immunity and tumor progression. Here, we investigate the roles of M1 (tumoricidal) and M2 (tumor permissive) macrophages in primary and metastatic sarcoma samples.

Methods: This study utilized sets of 3 tissue arrays each for primary and metastatic tumor samples. 13 patients with primary tumors and 21 patients with metastatic tumors were used for analysis. 61 primary and 41 metastatic tumor samples were observed. Vectra Polaris microarrays were used to investigate macrophage subsets (CD68+/HLADR+/CD163- for M1, CD68+/HLADR-/CD163+ for M2). Cell counts per core and antibody were collected for bioinformatics analysis using R software. M2/M1 cell density ratios were calculated, and distinct groups were identified.

Results: The M2/M1 cell density ratios in the primary samples ranged from 5.8 to 237.1. The low (5.8-63.2), medium (73.7-124.7), and high (107.8-237.1) ratio groups were statistically significant from each other. The M2/M1 cell density ratios in the metastatic samples ranged from 0.0 to 37.5. The low (0.0-1.0), medium (1.0-5.0), and high (>5.0) ratio groups were statistically significant from each other. Patient outcomes were identified, and unique patient characteristics were noted for each ratio.

Conclusion: We demonstrate for the first time in primary and metastatic osteosarcoma samples that distinct macrophage populations arise and form unique tumor microenvironments. Importantly, we observe M2/M1 ratios that are several times higher than in the primary samples. This indicates a more pro-tumor environment in the primaries than the metastases.