Myeloid-derived suppressor cells and plasmacytoid dendritic cells are associated with oncogenesis of oral squamous cell carcinoma

Abstract

Myeloid-derived suppressor cells (MDSCs) help establish the tumor microenvironment by suppressing T-cell response in tumor-bearing hosts. Plasmacytoid dendritic cells (pDCs) activate antigen-specific T cells, thereby, maximizing their antitumor effects. IDO1 is associated with both MDSCs and pDCs and plays a major role in the formation of the tumor-mediated immunosuppressive environment. We utilized immunohistochemistry to examine the involvement of IDO1 in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs, precancerous lesions). We examined the expression of MDSC markers, CD11b and CD33, as well as pDC markers, CD303 and IDO1, in 60 OSCC and 45 precancerous lesion specimens and analyzed their association with clinicopathological parameters. Expression of these biomarkers identifying MDSCs and pDCs was high in precancerous lesions in patients with severe dysplasia and OSCC. While detecting pDCs, high CD303 and IDO1 expression levels were frequently observed in moderately or poorly differentiated OSCCs. CD11b, CD33, and CD303 levels were significantly correlated with the mode of invasion; CD33 was correlated with OSCC invasion depth while the other three markers tended to be highly expressed in superficial cancer cases showing microinvasion. Expression levels of all four biomarkers were significantly associated with the cancerization of OPMDs to OSCCs. We show, for the first time, that the infiltration of MDSCs and pDCs is significantly associated with progression of premalignant lesions to OSCC. This suggests that these cells may act as prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches that control each of these immunosuppressive cells may protect against progression to malignancy.

Keywords: myeloid-derived suppressor cell; oral cancer; oral epithelial precursor lesion; plasmacytoid dendritic cells; squamous cell carcinoma.

FIGURE 1

Expression of CD11b, CD33, CD303, and IDO1 in oral squamous cell carcinoma (OSCCs) and precancerous lesion tissues was analyzed via immunohistochemistry. Myeloid‐derived suppressor cells (MDSCs) with CD11b and CD33 were detected among the stromal cells. CD303‐positive plasmacytoid dendritic cells (pDCs) were present in the stromal cells near the tumor cells. IDO1 was found in the stromal cells near the tumor cells as well as in the forefront parts of the tumor cells; magnification, ×200. Scale bar: 200 μm.

FIGURE 2

Representative images of CD11b, CD33, CD303, and IDO1 expression in precancerous lesions and OSCCs. The expression of CD11b, CD33, CD303, and IDO1 tended to increase with malignancy of oral epithelial legions. OSCCs, oral squamous cell carcinoma; HP, hyperplasia; LD, low‐grade epithelial dysplasia; HD, high‐grade epithelial dysplasia; magnification, ×100. Scale bar: 100 μm.