Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis

• Published in: Oral oncology 2020-05, Vol.104, p.104616-104616, Article 104616
• Main Authors: Liou, Anthony Kian-Fong, Soon, Gwyneth, Tan, Louise, Peng, Yang, Cher, Boon Meng, Goh, Boon Cher, Wang, Shi, Lim, Chwee Ming
• Format: Article
• Language: English
• Subjects: Female; Humans; Immunohistochemistry; Interleukin-18; Interleukin-18 - immunology; Interleukin-18 - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - immunology; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - pathology; Natural killer cells; Prognosis; Programmed cell death 1 receptor; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - metabolism; Survival Analysis; Tumor microenvironment; Tumor-infiltrating lymphocytes
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2020.104616

•Tumor infiltrating NK cells has a bimodal distribution in NPC with prognostic significance.•Patients with high levels of tumour infiltrating NK cells (NKhigh) have a worse prognosis.•Higher percentage of NK cells in NKhigh cohort expressed PD-1.•IL-18 alone within the tumor microenvironment induces PD-1 expression on NK cells in a dose-dependent manner. Characterisation of tumor-infiltrating lymphocytes (TILS) population for cancer prognostication has enabled deeper understanding of tumor immune interactions in cancer immunology. We aim to examine the significance of both the density and functional status of NK cells in a cohort of Epstein Barr Virus (EBV) associated Nasopharyngeal Cancer (NPC) patients. NK TILS of 50 NPC samples were quantified on immunohistochemistry and the density of NK TILS was correlated with clinical outcomes. Next, NK cells and a panel of cytokines of 10 newly diagnosed NPC patients were characterized in both NPC tissue and peripheral circulation. Exhausted NK cells were identified using co-expression of PD-1 and/or Tim-3. Comparison of percentage of NK cells in NPC and healthy controls was performed using student t-test for two groups; and a p value of less than 0.05 values was considered significant. NK TILS exhibited a bimodal distribution; with the NKhigh cohort demonstrating a poorer 2-year overall survival rate (p