Circulating and tumor-infiltrating myeloid cells predict survival in human pleural mesothelioma

Cancer. 2011 Nov 15;117(22):5234-44. doi: 10.1002/cncr.26143. Epub 2011 Apr 26.


Background: Malignant pleural mesothelioma (MPM) tumor cells produce copious amounts of myeloid cell-stimulating factors. The current study examined the prognostic significance of circulating monocytes and tumor-infiltrating macrophages on overall survival in patients with MPM.

Methods: The authors retrospectively reviewed 667 patients with MPM who underwent cytoreductive surgery at the Brigham and Women's Hospital in Boston, Massachusetts between 1989 and 2009. Kaplan-Meier and Cox proportional hazards models were used to determine the impact of preoperative circulating monocytes on overall survival. Immunohistochemical staining for CD68 was performed on a tissue microarray of MPM tumors from 52 patients undergoing cytoreductive surgery. The phenotype of circulating monocytes and tumor-infiltrating macrophages in 7 additional patients was determined by flow cytometry.

Results: The median survival for all patients was 13.4 months, and 35% of patients had tumors of nonepithelial histology. For patients with nonepithelial compared with epithelial tumors, survival was significantly worse (9.3 months vs 16.6 months; P < .0001), the number of monocytes was significantly higher (580 ± 20 cells/μL vs 520 ± 10 cells/μL; P = .002), and higher monocyte counts were associated with higher tumor stage. Increasing monocyte counts were correlated with poor survival for all patients with MPM. Within MPM tumors, macrophages comprised 27% ± 9% of the tumor area and demonstrated an immunosuppressive phenotype with high expression of CD163, CD206, and interleukin-4 receptor α. The degree of macrophage infiltration was found to be negatively correlated with survival in patients with nonepithelial (P = .008) but not those with epithelial (P = .7) MPM, independent of disease stage.

Conclusions: Higher numbers of circulating monocytes are associated with poor survival in all patients with MPM and higher densities of tumor-infiltrating macrophages are associated with poor survival in patients with nonepithelial MPM. Both may enable a novel target for immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Humans
  • Macrophages / pathology
  • Male
  • Mesothelioma / mortality*
  • Mesothelioma / pathology*
  • Middle Aged
  • Myeloid Cells / pathology*
  • Neoplastic Cells, Circulating / pathology*
  • Pleural Neoplasms / mortality*
  • Pleural Neoplasms / pathology*
  • Prognosis
  • Survival Rate