Affiliation:
1. Department of Integrative Pathology Jichi Medical University Shimotsuke Tochigi Japan
2. Department of Otolaryngology‐Head and Neck Surgery Jichi Medical University Saitama Medical Center Saitama Japan
3. Department of Pathology, Faculty of medicine University of Tsukuba Tsukuba Ibaraki Japan
4. Department of Otolaryngology‐Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan
5. Department of Otolaryngology‐Head and Neck Surgery Jichi Medical University Shimotsuke Tochigi Japan
6. Department of Dentistry, Oral and Maxillofacial Surgery Jichi Medical University Saitama Medical Center Saitama Japan
Abstract
AbstractBackgroundCancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis.MethodsFirst, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune‐related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death‐ligand 1 (PD‐L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed.ResultsAmong the novel OSCC‐specific immune‐related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T‐cell subsets and CD20‐positive cells were less common in the advanced stages, whereas CD163‐positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD‐L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence‐free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD‐L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence‐free survival.ConclusionsThe stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer‐associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.
Funder
Japan Society for the Promotion of Science