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Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma
  1. Marc L Ooft1,
  2. Jolique A van Ipenburg2,
  3. Maxime E Sanders1,
  4. Mariette Kranendonk1,
  5. Ingrid Hofland3,
  6. Remco de Bree4,
  7. Senada Koljenović2,
  8. Stefan M Willems1
  1. 1Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
  3. 3Department of Pathology, Core facility Molecular pathology and Biobanking, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, the Netherlands
  4. 4Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands
  1. Correspondence to Stefan M Willems, Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; S.M.Willems-4{at}umcutrecht.nl

Abstract

Aims Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, and both correlate with worse survival in head and neck cancers. However, the prognostic role of TAM and Tregs in nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences in TAMs and Tregs in different NPC subtypes, and their prognostic significance.

Methods Tissue of 91 NPCs was assessed for TAMs and Tregs by determination of CD68, CD163, CD206 and FOXP3 expression in the tumour microenvironment. Clinicopathological correlations were assessed using Pearson X2 test, Fisher’s exact test, analysis of variance and Mann-Whitney U test. Survival was analysed using Kaplan-Meier curves and Cox regression.

Results CD68 and FOXP3 counts were higher in Epstein-Barr virus (EBV)-positive NPC, while CD68−/FOXP3−, CD163+/FOXP3− and CD206+/FOXP3− infiltrates were more common in EBV-negative NPC. In the whole NPC group, CD68−/FOXP3− correlated with worse overall survival (OS), and after multivariate analysis high FOXP3 count showed better OS (HR 0.352, 95% CI 0.128 to 0.968). No difference in M2 counts existed between EBV-positive and negative NPC.

Conclusions FOXP3, a Treg marker, seems to be an independent prognostic factor for better OS in the whole NPC group. Therefore, immune-based therapies targeting Tregs should be carefully evaluated. M2 spectrum macrophages are probably more prominent in EBV-negative NPC with also functional differences compared with EBV-positive NPC.

  • oncology
  • immunohistochemistry
  • immunopathology
  • head and neck cancer

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Footnotes

  • Handling editor Runjan Chetty.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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