22 Prognostic impact of tumor associated macrophages and tumor infiltrating lymphocytes in head and neck cancer treated with primary chemoradiotherapy

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We investigated the prognostic role of tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT). The expression of CD3+, CD4+, CD8+, FOXP3+, CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n = 106 pre-treatment tumor biopsy samples and was correlated with clinicopathological characteristics, including HPV-p16-status, T-stage, N-stage, grading, tumor localization, age and sex as well as local failure free- (LFFS), distant metastases free- (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 to their matched primary tumors. All local recurrences occurred in the high radiation dose region (⩾70 Gy). With a median follow-up of 40 months, OS at 2 years was 60.5%. Low CD3 and CD8 as well as high CD68 and CD163 expression in primary tumors were associated with decreased OS, PFS, LPFS and DMFS. After multivariate analysis all of the above markers remained significant or marginally significant for these endpoints (such as for OS: p = 0.009, p = 0.011, p = 0.002 and p = 0.052 for CD3, CD8, CD68 and CD163 respectively). On the contrary CD4, FOXP3 and CD11b did not have any prognostic impact. 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 to their matched primary samples. Altogether, baseline numbers of M2-TAMs and cytotoxic lymphocytes seem to be important prognostic parameters in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of the immune system in mediating response to CRT in patients with HNSCC and need further evaluation in a prospective trial.