Immunological and Genetic Characterization of Patients With Head and Neck Cancer who Developed Recurrence

Autor: Kazuaki, Yasui, Ryota, Kondou, Haruo, Miyata, Akira, Iizuka, Tadashi, Ashizawa, Takeshi, Nagashima, Keiichi, Ohshima, Kenichi, Urakami, Koji, Muramatsu, Takashi, Sugino, Ken, Yamaguchi, Hirofumi, Ogawa, Tsuyoshi, Onoe, Hideyuki, Harada, Hirofumi, Asakura, Shigeyuki, Murayama, Tetsuo, Nishimura, Seiya, Goto, Shinichi, Okada, Takashi, Mukaigawa, Satoshi, Hamauchi, Tomoya, Yokota, Yusuke, Onozawa, Yasuto, Akiyama
Rok vydání: 2022
Předmět:
Zdroj: Anticancer Research. 42:4417-4428
ISSN: 1791-7530
0250-7005
DOI: 10.21873/anticanres.15942
Popis: 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.The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated 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).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 epithelial-mesenchymal 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.A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-β1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.
Databáze: OpenAIRE
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