Abstract 5869: The concordant disruption of B7/CD28 immune regulators predicts the prognosis of oral carcinoma

Abstract

Abstract Immune-escape is a critical factor determining the survival of malignancies including oral squamous cell carcinoma (OSCC). The immune escape of cancer cells may be driven by B7/CD28 family members and others on the tumor cells that form ligand-inhibitory receptor complexes with immune cells. Since the family members of B7/CD28 can functionally compensate, the concomitant disruption of multiple B7/CD28 family members in OSCC pathogenesis remains elusive. RNAseq performed on OSCC and paired oral mucosa retrieved the transcriptome of OSCC, and algorithms signified the general alterations of T cell population and the increase of macrophage population in tumors relative to controls. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276 and CTLA4, and downregulation of L-ICOS in OSCC relative to normal mucosa was noted. In addition, there was a high concordance in the expression profile across the dysregulated regulators. The co-upregulation of CD276 and CTLA4 was associated with the decrease of T helper and NK cell population, and the increase of Treg and myeloid dendritic cell population. Interestingly, tumors harboring higher PD-L1 and/or PD-L2 expression accompany with lower ICOS or PD1 expression exhibited worse prognosis. In combination with these immunity features in primary tumors, the survival of patients with lymph node metastasis was further worsened. In the isografic models of murine OSCC cell lines, the decrease of CD4+T population in the lymph node and increase of myeloid dendritic cell population in the spleen were induced in the host mice. Many miRNAs are involved in the modulation of immune escape for malignancies. With the treatment of inhibitors against oncogenic miRNAs which enabled the OSCC suppression, the inhibitors of miR-146a and miR-211 also resulted in the down-regulation in the protein expression of multiple B7/CD28 members. This study concludes the eminent co-disruption of B7/CD28 members in OSCC tumors, which would confound the patient survival. The efficacy of miRNA inhibitors in abrogating oncogenicity and B7/CD28 members could be a therapeutic strategy. Citation Format: Sih-Rou Chang. The concordant disruption of B7/CD28 immune regulators predicts the prognosis of oral carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5869.