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

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.