Positive PD-L1 expression was significantly associated with poor disease free survival of SGCs, suggesting that antibody therapies targeting PD-1/PD-L1 may have potential application in SGCs. J. Surg. Oncol. 2016;114:36-43. © 2016 Wiley Periodicals, Inc.

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Background/Aim: The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated. Patients and Methods: The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancerassociated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC). Results: Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31. 6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-β1-PAX7 pathway and epithelialmesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred. Conclusion: A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-β1-PAX7mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer; however, a reduction in the rate of its recurrence remains challenging; the 5-year survival rate of patients with HNSCCs is reported to be only 50-60% (1, 2). The recurrence rate is high, approximately 30%, which indicates not only high mortality and difficulty in treatment, but also the genetic complexity affecting cancer progression 4417

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