title: M2-polarized macrophages contribute to the decreased sensitivity of EGFR-TKIs treatment in patients with advanced lung adenocarcinoma.
abstract: Previous study has revealed that tumor-associated macrophages (TAMs) correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). In the present study, we further determined that M2-TAMs, but not M1-TAMs, are related to the treatment response to EGFR-TKIs in advanced NSCLC and may be an independent predictor of survival. Eighty-eight advanced lung adenocarcinoma patients treated with a second-line EGFR-TKI were involved in this study. M2-TAMs counts but not M1-TAMs were significantly higher in patients with progressive disease than in those without (P < 0.001). A trend also remained in patients with known EGFR status (n = 61) and those with mutant EGFR (n = 49). High M2-TAMs counts were shown to be significantly related to poor progression-free survival (PFS) and overall survival (OS) in all patients, or subsets of patients with known EGFR status or patients with EGFR mutation (all P < 0.05). Multivariate Cox analyses showed that high M2-TAMs counts and EGFR mutations were both independent factors associated with PFS and OS (P < 0.05). Overall, we revealed that M2- but not M1-TAMs are related to the response of EGFR-TKIs treatment irrespective of EGFR mutation and can independently predict survival in advanced lung adenocarcinoma treated with a second-line EGFR-TKI.
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, 627 Wuluo Road, Wuhan, 430070, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.forename: Wuling
authors.initials: W
authors.lastname: Ou
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Rao
authors.forename: Jianfei
authors.initials: J
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors