Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences

Br J Cancer. 2014 Oct 14;111(8):1509-18. doi: 10.1038/bjc.2014.446. Epub 2014 Aug 5.

Abstract

Background: We investigated the prognostic role of tumour-associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).

Methods: The expression of CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n=106 pre-treatment tumour biopsy samples and was correlated with clinicopathological characteristics, including T-stage, N-stage, grading, tumour localisation, age and sex as well as local failure-free survival (LFFS), distant metastases-free survival (DMFS), progression-free (PFS), and overall survival (OS). Finally, TAMs expression and vessel density (CD31) were examined in n=12 available early local recurrence samples and compared with their matched primary tumours . The diagnostic images and radiotherapy plans of these 12 patients were also analysed. All local recurrences occurred in the high radiation dose region (⩾70 Gy).

Results: With a median follow-up of 40 months, OS at 2 years was 60.5%. High CD163 expression in primary tumours was associated with decreased OS (P=0.010), PFS (P=0.033), LFFS (P=0.036) and DMFS (P=0.038) in multivariate analysis. CD163 demonstrated a strong prognostic value only in human papillomavirus (p16(INK4))-negative patients. Early local recurrence specimens demonstrated a significantly increased infiltration of CD11b+ myeloid cells (P=0.0097) but decreased CD31-positive vessel density (P=0.0004) compared with their matched primary samples.

Conclusions: Altogether, baseline CD163 expression predicts for an unfavourable clinical outcome in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of TAMs in mediating response to CRT in patients with HNSCC.

MeSH terms

  • Antigens, CD / immunology*
  • Antigens, Differentiation, Myelomonocytic / immunology*
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow Cells / immunology*
  • CD11b Antigen / immunology*
  • Female
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Radiotherapy*
  • Receptors, Cell Surface / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD11b Antigen
  • CD163 antigen
  • ITGAM protein, human
  • Receptors, Cell Surface