Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma

Objective. The purpose of this study is to identify the immuno-oncologic (IO) signature at the surgical tumor margin (TM) of oral squamous cell carcinoma (OSCC) that is involved in the process of malignant transformation. Study Design. Under institutional review board approval, TM of 73 OSCC were investigated using immunohistochemistry for the immune biomarker, programmed death ligand-1 (PD-L1). NanoString 770 IO-focused gene set was analyzed in 5 pairs of TM and invasive tumor (T). PD-L1 regulation in response to interferon-gamma (IFN-y) was investigated in an oral potentially malignant cell line (OPMC). Results. Programmed death ligand-1 expression in the epithelial margin directly correlated with its expression in the underlying immune cells (P = .0082). Differential gene expression showed downregulation of PD-L1 and IFN-y 6 gene signature in the TM relative to T pair.CD8 and macrophages were higher in TM. CNTFR, LYZ, C7, RORC, and FGF13 downregulation in T relative to TM. TDO2, ADAM12, MMP1, LAMC2, MB21D1, TYMP, OASL, COL5A1, exhausted_CD8, Tregs,and NK_CD56dim were upre-gulated in T relative to TM. Finally, IFN-y induced upregulation of PD-L1 in the OPMC. Conclusions. Our work suggests a role for IFN-y in PD-L1 upregulation in OPMC and presents novel IO transcriptional signatures for frankly invasive OSCC relative to TM. (Oral Surg Oral Med Oral Pathol Oral Radiol 2023;136:612-622)