title: Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival.
abstract: There is a marked survival advantage for patients with nonsmall cell lung cancer (NSCLC) expressing high numbers of macrophages in their tumour islets. The primary aim of the present study was to determine the immunological phenotype of NSCLC-associated macrophages. CD68(+) macrophages expressing markers of a cytotoxic M1 phenotype or a noncytotoxic M2 phenotype were identified in the islets and stroma of surgically resected tumours from 20 patients with extended survival (median 92.7 months) and 20 with poor survival (median 7.7 months), using immunohistochemistry. The islet density of both M1 and M2 macrophages was markedly increased in extended compared with poor survival patients. In the extended survival group, M1 islet density was significantly increased compared with M2 density, 70% of islet macrophages were positive for M1 markers versus 38% for M2, and the islet:stromal ratio of M1 macrophages was markedly increased compared with M2. The 5-yr survival for patients with above and below median expression of M1 macrophages in the islets was >75 and <5%, respectively. Macrophages infiltrating the tumour islets in nonsmall cell lung cancer were predominantly of the M1 phenotype in patients with extended survival. The survival advantage conferred by islet macrophage infiltration may be related to their cytotoxic antitumour activity.
authors.affiliation: Institute for Lung Health, Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. cohri@doctors.org.uk
authors.forename: C M
authors.initials: CM
authors.lastname: Ohri
authors.forename: A
authors.initials: A
authors.lastname: Shikotra
authors.forename: R H
authors.initials: RH
authors.lastname: Green
authors.forename: D A
authors.initials: DA
authors.lastname: Waller
authors.forename: P
authors.initials: P
authors.lastname: Bradding
mesh_terms: D000368:Aged; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II