Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer

Cancer. 2008 Sep 15;113(6):1387-95. doi: 10.1002/cncr.23712.


Background: The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients.

Method: The authors performed an immunohistochemical study to identify and count the number of CD68(+) macrophages, c-kit(+) mast cells, and CD8(+) T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis.

Results: There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests < stroma cases median survival time (MST 440 days vs 199 days; P < .0001). Patients with more tumor-infiltrating CD8(+) T cells in cancer nests than in cancer stroma (CD8(+) T cells: nests > stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8(+) T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome.

Conclusions: Evaluation of the numbers of macrophages and CD8(+) T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Mast Cells / immunology
  • Mast Cells / pathology
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Stromal Cells / immunology
  • Stromal Cells / pathology
  • Survival Rate


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human