The expression of nicotinic acetylcholine receptor subunits and their associations with local immune cells and prognosis in oral squamous cell carcinoma

Abstract

BackgroundNicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels that may be responsible for cancer cell proliferation, epithelial–mesenchymal transition (EMT), and immune regulation. However, little is known about the associations of different nAChR subunits with tumor microenvironment in oral squamous cell carcinoma (OSCC).MethodsWe retrospectively reviewed pathology samples from 75 OSCC patients by immunohistochemistry. In addition, a cohort of 307 OSCC patients in The Cancer Genome Atlas was analyzed.ResultsSubunit α1 was specific to peri‐OSCC skeletal muscle. Increased α1 was associated with increased CD44 (cancer stem cells), increased CD3 and 8 (T cells), increased CD56 and 16 (natural killer cells), a decreased T stage, and an increased N stage. Increased α3 was associated with increased CD56 and 16. Increased α5 was associated with decreased CD3, 8, and 56, a decreased T stage, an increased N stage, worse survival, and decreased epithelial features. Increased α7 was associated with increased CD3, 8, 56, and 16, decreased tumor/peritumor ratios of CD3, 8, and 56 immune cells, and increased epithelial features. Increased local immune cells were associated with a better prognosis.Conclusionsα5 is the only subunit associated with decreased local immune cells and worse survival, while α1, α3, and α7 are associated with increased local immune cells in OSCC. α5 and α7 are correlated with different EMT states to be mesenchymal‐like and epithelial‐like OSCC, respectively. Protein expression data of the nAChR subunits, complementary to gene expression data, could provide meaningful information regarding the EMT status of OSCC associated with immune responses and prognosis.

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“…Moreover, a number of studies have reported that α7 nAChR affected the interaction between immune cells. Activated α7 nAChR was strongly associated with an increased immune cell infiltration in the tumor microenvironment and a decreased tumor/peritumor ratio of T and NK cells [ 74 ]. These previous findings indicate that nAChR is closely related to tumor immune response.…”

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