Abstract
BACKGROUND: This study aimed to assess the prognostic and predictive implications of CD47, CD68, and CD163, biomarkers of tumor-associated macrophages (TAMs), on the treatment efficacy and clinical outcomes of nasopharyngeal carcinoma (NPC). Additionally, the prognostic value of TAM-related indices, such as the monocyte-to-lymphocyte ratio (MLR) and monocyte-to-albumin ratio (MAR), was evaluated. METHODS: A retrospective cohort of 54 patients with locally advanced or oligometastatic NPC treated with concurrent chemoradiotherapy (CCRT), with or without induction chemotherapy, was analyzed. Patients were categorized based on the cumulative expression scores for CD47, CD68, and CD163: negative/low (0-3 points) and high (4-6 points). MLR and MAR were also stratified as low MLR (<0.545) vs. high MLR (≥0.545) and low MAR (<16.145) vs. high MAR (≥16.145). The primary endpoint was overall survival (OS). RESULTS: High CD47, CD68, and CD163 expression levels were correlated with advanced clinical stage, reduced CCRT response, and elevated MLR and MAR. These TAM biomarkers were linearly correlated with each other and with established risk factors such as advanced age and elevated EBV-DNA levels. Kaplan-Meier analysis revealed that patients with low TAM expression had significantly longer OS and progression-free survival (PFS) than those with high TAM expression. Multivariate analysis identified high CD163, MLR, and MAR levels as independent adverse prognostic factors for OS. Elevated MLR is an independent risk factor for both OS and PFS in patients with NPC. CONCLUSIONS: CD47, CD68, and CD163 are significant prognostic markers in NPC, with higher levels being associated with poorer OS and PFS. Elevated MLR and MAR values also predict worse outcomes, underscoring their value as prognostic tools. CD163 and MLR are particularly strong predictors, highlighting the crucial role of TAMs in NPC management and suggesting that CD163 is a potential therapeutic target within the immune checkpoint pathway.