Prognostic Relevance of Macrophage Phenotypes in High-grade Oral Tongue Squamous Cell Carcinomas

Abstract

Tumor-associated macrophages (TAMs) are part of the tumor microenvironment, broadly divided into M1 and M2 phenotypes. M1 macrophages, commonly identified by staining the CD11c antigen, have an antitumour immunity role, while M2 macrophages, expressing the CD163 antigen, are involved in tumor progression. Little is known about M1 and M2 phenotypes in the context of the oral tongue squamous cell carcinomas (OTSCC), a subgroup of oral cancer with peculiar clinical behavior. This study evaluated the macrophage polarization in OTSCC specimens to examine their prognostic relevance. To this end, specimens from 71 OTSCC patients graded as G1 or G3 were investigated for CD11c and CD163 expression. Immunohistochemical staining of TAMs was evaluated in tumor nests, tumor inflammation area (TIA), and tumor stroma. To analyze the expression of CD11c and CD163, the percentage of positive cells was scored as 0 (negative), 1 (<10%), 2 (11% to 50%), 3 (51% to 80%), and 4 (>80%). The staining intensity was scored as 0 (negative), 1 (weak), 2 (moderate), and 3 (intense). Higher expression of both CD163+ and CD11c+ macrophages in inflammation area positively correlated with G3 grade, both in extension and intensity. Focusing on G3 tumors, survival curves showed better disease-free survival in patients with high CD11c expression in the TIA. Presence of CD163 expression in TIA was associated with worse disease-free survival. This study evaluated, for the first time, the distribution of M1 and M2 macrophages in relation to the pathologic grade in OTSCC, highlighting the prognostic relevance of analyzing the localization of TAMs.