Towards Next Generation Biomarkers in Natural Killer/T-Cell Lymphoma

Natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus-associated non-Hodgkin lymphoma linked to an aggressive clinical course and poor prognosis. Despite an improvement in survival outcomes with the incorporation of novel agents including immune checkpoint inhibitors in the treatment of NKTCL, a significant proportion of patients still relapse or remain refractory to treatment. Several clinical prognostic models have been developed for NKTCL patients treated in the modern era, though the optimal approach to risk stratification remains to be determined. Novel molecular biomarkers derived from multi-omic profiling have recently been developed, with the potential to improve diagnosis, prognostication and treatment of this disease. Notably, a number of potential biomarkers have emerged from a better understanding of the tumor immune microenvironment and inflammatory responses. This includes a recently described 3'UTR structural variant in the PD-L1 gene, which confers susceptibility to checkpoint immunotherapy. In this review, we summarize the biomarker landscape of NKTCL and highlight emerging biomarkers with the potential for clinical implementation.