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. 2020 Jul 2;12(7):1764.
doi: 10.3390/cancers12071764.

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Faustino J Suárez-Sánchez  1 , Paloma Lequerica-Fernández  2   3 , Julián Suárez-Canto  1 , Juan P Rodrigo  3   4   5   6 , Tania Rodriguez-Santamarta  3   7 , Francisco Domínguez-Iglesias  1 , Juana M García-Pedrero  3   6 , Juan C de Vicente  3   5   7
Affiliations

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Faustino J Suárez-Sánchez et al. Cancers (Basel). .

Abstract

Tumor-associated macrophages (TAMs) can be polarized into antitumoral M1 and protumoral and immunosuppressive M2 macrophages. This study investigated the clinical relevance of TAM infiltration in oral squamous cell carcinoma (OSCC), evaluating CD68 (M1 and M2 macrophage marker) and CD163 expression (M2 macrophage marker) in the tumor nests and surrounding stroma. Immunohistochemical analysis of both stromal/tumoral CD68+ and CD163+ TAMs was performed in paraffin-embedded tissue specimens from 125 OSCC patients, and correlated with clinical data. Potential relationships with the expression of cancer stem cell (CSC) markers and PD-L1 in the tumors were also assessed. Stromal CD163+ infiltration was significantly associated with the tumor location in the tongue, and stromal and tumoral CD68+ and CD163+-infiltrating TAMs were more abundant in nonsmokers and non-alcohol-drinkers. Strikingly, this study uncovers an inverse relationship between CD68+ and CD163+ TAMs and CSC marker expression (NANOG and SOX2) in OSCC. High infiltration of CD163+ TAMs in both tumor and stroma was strongly and significantly correlated with the absence of NANOG expression. Moreover, infiltration of both CD68+ and CD163+ TAMs was also significantly associated with high tumor expression of PD-L1. Our results suggest that there is a link between TAM infiltration and immune escape in OSCC.

Keywords: CD163; CD68; NANOG; PD-L1; oral squamous cell carcinoma; tumor microenvironment; tumor-associated macrophages.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical analysis of CD68 expression in OSCC tissue specimens. (A) Representative example of positive CD68 expression in tumor-associated macrophages (TAMs) both in tumor nests and in the stroma (original magnification ×100). (B) CD68 cytoplasmic staining in cells identified as TAMs (original magnification ×400).
Figure 2
Figure 2
Immunohistochemical analysis of CD163 expression in OSCC tissue specimens (A) CD163 expression both in stromal and tumoral TAMs (original magnification ×100). (B) CD163 expression in stromal TAMs (original magnification ×400).
See this image and copyright information in PMC

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