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

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 (p16INK4)-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.

Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma

“…The prognostic importance of tumor infiltration with CD3 þ and CD8 þ cells has been demonstrated in breast, esophageal, lung, ovarian, colon, and anal cancers (31). In addition, Balermpas and colleagues (30) reported that the intratumoral localization of TILs (in close proximity of tumor cells, in the tumor stroma and in the periphery) influences their prognostic impact. Recent studies by Taube and colleagues (20) and Tumeh and colleagues (32) have also demonstrated that the location of T-cell infiltrate and PD-L1-expressing cells within a tumor specimen is of particular importance; detection of CD8 þ TILs and PD-L1-expressing cells at the invasive margin was associated with better response to therapy.…”

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

“…24 In addition, Balermpas and colleagues reported that the intratumoral localization of TILs influences their prognostic impact. 25 Tumeh et al suggest that the presence of TILs is not a dichotomous variable and that the density and location of TILs and their interaction with the PD-L1-positive tumor microenvironment should be considered.…”

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

“…M1 macrophages contribute to immune response against malignant cells by activating Th1 cells, whereas M2 macrophages produce an anti-inflammatory response via cytokine release that promotes tumor growth (52). In HNSCC, TAMs are associated with worse outcome postsurgery and chemoradiotherapy (53,54). Finally, Tregs, often expressed in patients with HNSCC, can suppress immune responses via production of IL-10 and TGF-β, using up environmental T-cell survival factors, and dysregulating local T cells (55).…”