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Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Our study investigated whether tumor‐associated macrophages (TAMs) in advanced non‐small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first‐line) with an EGFR‐TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR‐TKI treatment, response was observed in 55 (51%) patients, and the median follow‐up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n = 59) and those with wild‐type EGFR (n = 20). High TAM counts, among other factors (e.g., wild‐type EGFR), were significantly related to poor progression‐free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87–22.4; p = 0.0001 and OR, 0.03; 95% CI, 0.003–0.31; p = 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08–6.5; p = 0.03 and OR, 0.14; 95% CI, 0.03–0.56; p = 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR‐TKI.