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Tumor-associated macrophages (TAMs) play an emerging role in tumor progression by creating an immunosuppressive tumor microenvironment. Therefore, we investigated TAM numbers and their activation (M1/2) in primary (p-) and recurrent (r-) meningiomas and evaluated their impact on survival. Presence of TAMs was analyzed in 195 clinically well-annotated cases (WHO°I n = 43, WHO°II n = 95, WHO°III n = 57; pMGM n = 120, rMGM n = 75). TAMs were quantified by a semiautomated analysis on whole tissue sections stained by multicolor immunofluorescence for CD68 as general TAM marker, and for CD163 and CD204 as M2 marker. CD68+ macrophages positive for either CD163 or CD204 were regarded as M2-polarized TAMs. Furthermore, concentration of 27 immune-relevant cytokines and chemokines from meningioma tissue samples (n = 46) were assessed by Luminex analysis. Median TAM infiltration accounted for 2.47% per total cell count in pMGM and 3.22% in rMGMs. Although no significant WHO°-dependent changes regarding TAM numbers were observed, high numbers of TAMs were associated with shorter progression-free survival (PFS) independent of prognostic confounding variables such as WHO, sex and age. In pMGMs, proportion of M2-polarized TAMs was significantly increased in WHO°II and WHO°III tumors compared to WHO°I (P = 0.001 and P = 0.03, respectively). Luminex data revealed a WHO°-dependent increase of IL-8, IL-10, and IL-12p70. Tissue samples containing higher numbers of TAMs demonstrated significant elevated concentrations of interleukin-1 family members (IL-1β, IL-1Ra), and G-CSF. Furthermore, upregulation of IL-1β and IL-1Ra resulted in shorter overall survival of patients (P = 0.049, P = 0.006, respectively). Taken together, we identified higher numbers of TAMs as an independent prognostic factor for shorter progression-free survival in meningioma patients. This was associated with increased levels of the interleukin-1 family members IL-1β and IL-1Ra and a shorter overall survival, indicating an important function in the tumor microenvironment.

TAMI-61. TUMOR-ASSOCIATED MACROPHAGES ARE INDEPENDENT PROGNOSTIC MARKERS IN MENINGIOMAS