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Updated: Jun 30, 2026
Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells
Published on: February 2, 2011
Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients
Dahui Li1, Hongyuan Zou2, Mingyu Wang2
1Department of Lymphoma and Medical Oncology, Fudan University Shanghai Cancer Center, Research Center for Lymphoma, Fudan University, Shanghai 200032, China.
Rationale:
Natural killer/T-cell lymphoma (NKTCL) is an aggressive Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma with a poor prognosis. Recent genomic and transcriptomic studies of tumor tissues have advanced our understanding of NKTCL pathogenesis, but the systemic immune profile at initial diagnosis remains incompletely elucidated.
Methods:
In this study, we characterized the immune landscape of peripheral blood mononuclear cells (PBMCs) from 20 newly diagnosed NKTCL patients and 12 healthy donors using single-cell RNA sequencing and confirmed our results through flow cytometry and PrimeFlow.
Results:
We identified a distinct proliferative-NK/T (Proli-NK/T) cell subset in NKTCL, characterized by high expression of cell cycle-related genes but lacking a malignant phenotype. Additionally, we observed a reduction in total and classical memory B cells, accompanied by enrichment of apoptosis and cell differentiation signatures. NK cells showed increased expression of HLA class II and activation markers, along with enhanced predicted interactions with CD4+ T cells. The decrease of naive CD4+ T cells might imply their skewed differentiation into Th1 and Th17 cells, while expansion of granzyme K (GZMK+)-expressing CD8+ central memory T cells was associated with interferon-γ-driven responses. Patients with a high intracellular EBV load exhibited accumulation of highly cytotoxic CD56dim _PTPRCAP NK cells and GZMK+ GZMB+ CD8+ effector memory T cells, along with a marked depletion of memory B cells. This implies a correlation between intracellular EBV burden and peripheral immune dysregulation in NKTCL.
Conclusions:
We have uncovered the dynamic changes in PBMCs of newly diagnosed NK/T cell lymphoma patients and identified specific characteristics in patients with high intracellular EBV levels. Our findings provide new insights into the immunopathogenesis of NKTCL, offering valuable information for immune-based stratification and the development of therapeutic strategies.
