Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells.

OBJECTIVE: Accumulating evidence has demonstrated the protumor role of estrogen receptor (ER)-mediated signaling in multiple cancer types, which is distinct from this signaling in sex steroid-dependent organs. However, its role in oral squamous cell carcinoma (OSCC) remains unclear. STUDY DESIGN: We assessed the expression of ERα and ERß in human OSCC tissues by immunohistochemistry and evaluated the expression of both receptors in OSCC cell lines by immunoblotting and flow cytometry. To further assess the contribution of ER-mediated signals to oral cancer progression, proliferation, invasion, and chemosensitivity, cell lines were stimulated with the ER agonist ß-estradiol. RESULTS: Immunohistochemical analysis of OSCC tissues showed that ERß was present in the cytoplasm and nuclei of OSCC cells. In contrast, ERα was not detected in any of the cases analyzed. Additionally, the proliferation and invasiveness of OSCC cells were significantly elevated following stimulation with ß-estradiol. Chemotherapeutic agent-induced apoptosis of cancer cells was attenuated by pretreatment with ß-estradiol. CONCLUSIONS: ER-mediated signaling plays a crucial role in oral cancer progression by facilitating the proliferation, invasion, and chemoresistance of OSCC cells, indicating its potential for developing novel targeted therapies for this type of cancer.

Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b(+)Gr-1(+) cells and its contribution to immunosuppressive activity.

Cancer is often associated with dysregulation of both the humoral and cellular immune response, which in some instances is believed to result from changes in immune cell populations. For example, immunosuppressive CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been shown to proliferate in the tumor microenvironment and surrounding tissues, highlighting the relationship between tumor growth and impairment of the immune response. However, the role of myeloid-derived suppressor cells in cancer progression has not been fully characterized because these cells are heterogeneous with properties influenced by the type and location of the tumor. Here, we show that CD11b(+)Gr-1(+) cells are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. The phenotype and function of these cells varied depending on the tissue of origin. In particular, CD11b(+)Gr-1(+) cells in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, CD11b(+)Gr-1(+) cells from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of CD11b(+)Gr-1(+) cells in mice with oral squamous cell carcinoma. The data also indicate that PD-L1 expression in CD11b(+)Gr-1(+) cells contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.