Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

BMC Immunol. 2018 Jan 24;19(1):3. doi: 10.1186/s12865-018-0241-4.

Abstract

Background: Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients' survival.

Methods: Lung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually.

Results: Predominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05).

Conclusions: This study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients' survival.

Trial registration: ClinicalTrials.gov NCT01955343 , registered on September 27, 2013.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Macrophages / classification
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type II / immunology
  • Nitric Oxide Synthase Type II / metabolism
  • Prognosis
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CD68 antigen, human
  • Receptors, Cell Surface
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II

Associated data

  • ClinicalTrials.gov/NCT01955343