RARE-20TUMOR-ASSOCIATED MACROPHAGES ASSOCIATE WITH CEREBROSPINAL FLUID INTERLEUKIN-10 AND SURVIVAL IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)

Abstract

BACKGROUND: Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors. However, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. METHODS: Forty-seven patients with PCNSL who were treated with high-dose Methotrexate (MTX) and radiotherapy were retrospectively analyzed. CD68-, CD163-, and CD204-positive TAMs were evaluated using immunohistochemistry. Correlation between the infiltration levels of TAMs and clinicopathological parameters were analyzed. RESULTS: CD68-positive (CD68+), CD163 + , and CD204+ TAMs were diffusely infiltrated in PCNSL tissues. Age, performance status (PS), tumor number, and molecular subtype were not correlated with the infiltration levels of TAMs. Univariate analysis revealed that increased CD68+ and CD163+ TAMs were significantly associated with poorer progression-free survival (PFS). Moreover, increased CD68+ TAMs were significantly associated with shorter overall survival (OS). Multivariate analysis revealed that increased CD68+ TAMs was independent factors associated with PFS (Hazard ratio (HR) = 3.033, p = 0.015) and OS (HR = 2.620, p = 0.045). Because TAMs are known to produce various cytokines, we examined the relationship between cytokine levels in cerebrospinal fluid (CSF) and TAMs. CSF IL-10 levels were highly correlated with infiltration levels of CD163+ TAMs. CONCLUSIONS: Our results suggested that increased CD68+ TAMs is associated with poorer prognosis in PCNSL treated with high-dose MTX and radiotherapy. The level of CSF IL-10 may be a biomarker for infiltration levels of TAMs and prognosis of PCNSL patients.