CD206+ tumor-associated macrophages interact with CD4+ tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma

BackgroundTumor-associated macrophages (TAMs) are major component in the tumor microenvironment (TME) and play regulatory role in tumor progression. We aimed to investigate the infiltration and prognostic value of TAMs in laryngeal squamous cell carcinoma (LSCC) and to reveal the underlying mechanism of TAM subgroups in tumorigenesis.MethodsHematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. CD206 + /CD163 + and iNOS + TAM infiltrating profiles were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves based on the infiltration of TAMs were plotted using the Kaplan-Meier method. Infiltration of macrophages, T lymphocytes and their corresponding subgroups were analyzed in fresh LSCC tissue samples by flow cytometry.ResultsWe found that CD206(+) rather than CD163(+) M2-like TAMs were the most enriched population in the TME of human LSCC. CD206(+) macrophages localized mostly in the tumor stroma (TS) rather than the tumor nest (TN) region. In contrast, relatively low infiltration of iNOS(+) M1-like TAMs were found in the TS and almost none in the TN region. High level of TS CD206(+) TAM infiltration correlated with poor prognosis. Interestingly, we identified a HLA-DRhigh CD206(+) macrophage subgroup that was significantly associated with the tumor-infiltrating CD4(+) T lymphocytes and showed different surface costimulatory molecule expression than that of the HLA-DRlow/-CD206(+) subgroup. Taken together, our results indicate that HLA-DRhigh-CD206(+) is a highly activated subgroup of CD206 + TAMs that may interact with CD4 + T cells through MHC-II axis and promote tumorigenesis.