Abstract 1609: Peripheral NK-cell immunophenotypes predict progression in nasopharyngeal carcinoma patients

Abstract

Abstract Objective: The tumorigenesis is closely associated with the alteration in the expression of cell-surface proteins. As NK cells play a vital role in cancer immunotherapy, we thus conducted this study to characterize the immunophenotypes of circulating NK cells and to explore the association between NK phenotypes and disease prognosis. Methods: 249 nasopharyngeal carcinoma (NPC) patients and 11 healthy individuals were recruited in the study, whose peripheral blood samples were collected before treatment. Multi-color flow cytometry analysis was performed. The expression of four inhibitory receptors, PD-1, TIGIT, LAG-3, TIM-3, and four stimulatory receptors, NKp46, NKp30, CD226, NKG2D, were measured in three NK subsets, identified by the co-expression of CD56 and CD16 when gated on CD3-. The LASSO (least absolute shrinkage and selection operator) logistic regression model was used to screen out potential prognostic NK subtypes and calculate the NK-function index. Results: NPC patients exhibited distinct peripheral NK-cell distribution and altered expression of key receptors, as characterized by increased expression of PD-1 and TIGIT on CD56+CD16- cells and decreased expression of NKp46 on CD56+CD16- and CD56-CD16- cells. Four markers were selected from the LASSO model to calculate the NK-function index: PD1 and NKp46 on CD56-CD16+ NK cells, NKp46 on CD56+CD16- cells and NKG2D on CD56+CD16+ cells. Patients with low NK index had significantly shorter progression-free survival (PFS) and distant metastasis-free survival (DMFS), and the NK-function index was an independent prognostic factor for NPC patients. Conclusions: The immunophenotype of peripheral NK cells and its association with survival outcomes of NPC patients revealed its potential as a strong prognosticator for PFS and DMFS, and highlighted the important role of circulating immune environment, especially for the application of immunotherapy. Citation Format: Xiao-Yun Li, Zi-Jian Lu, Hai-Qiang Mai. Peripheral NK-cell immunophenotypes predict progression in nasopharyngeal carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1609.