TSENG-CHENG CHENChen C.-H.CHENG-PING WANGPEI-HSUAN LINTSUNG-LIN YANGPEI-JEN LOUJENG-YUH KOCHEN-TU WUYIH-LEONG CHANG2020-03-072020-03-0720172045-2322https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028829583&doi=10.1038%2fs41598-017-10386-y&partnerID=40&md5=f3480f122131fed2f503e05e8d32ff67https://scholars.lib.ntu.edu.tw/handle/123456789/473740Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC. ? 2017 The Author(s).[SDGs]SDG3biological marker; galectin; HAVCR2 protein, human; hepatitis A virus cellular receptor 2; LGALS9 protein, human; adult; aged; cancer grading; cancer staging; female; gene expression; human; immunohistochemistry; immunology; male; metabolism; middle aged; mortality; nasopharynx carcinoma; nasopharynx tumor; odds ratio; pathology; prognosis; proportional hazards model; tumor microenvironment; tumor recurrence; young adult; Adult; Aged; Biomarkers; Female; Galectins; Gene Expression; Hepatitis A Virus Cellular Receptor 2; Humans; Immunohistochemistry; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Odds Ratio; Prognosis; Proportional Hazards Models; Tumor Microenvironment; Young Adultjournal article10.1038/s41598-017-10386-y288710942-s2.0-85028829583