title: Tumor-associated macrophages correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer.
abstract: 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.
authors.affiliation: Pulmonary Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China.
authors.forename: Fu-Tsai
authors.initials: FT
authors.lastname: Chung
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Heh
authors.forename: Yao-Fei
authors.initials: YF
authors.lastname: Chan
authors.forename: Huan-Wu
authors.initials: HW
authors.lastname: Chen
authors.forename: Chih-Hsi
authors.initials: CH
authors.lastname: Kuo
authors.forename: Po-Hao
authors.initials: PH
authors.lastname: Feng
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lin
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chou
authors.forename: Hao-Cheng
authors.initials: HC
authors.lastname: Chen
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000032:analysis; D016896:Treatment Outcome; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases