Compromised activity of natural killer cells in diffuse large b-cell lymphoma is related to lymphoma-induced modification of their surface receptor expression

While natural killer (NK) cells are essential players in detection and elimination of malignant cells, these surveillance properties can be compromised by cancer cells. Since NK cell education primarily occurs in the bone marrow and lymphoid tissue, this process might be particularly affected by their infiltration with lymphoma cells. This study aimed to explore functional properties of diffuse large B-cell lymphoma (DLBCL) patient NK cells, which could potentially promote tumour immune evasion and disease propagation.NK cells isolated from the peripheral blood (PB) of 26 DLBCL patients and 13 age-matched healthy controls (HC) were analysed. The cytotoxic CD56^dim subtype was the only one identified in patients. Compared to HC, patient cells demonstrated low levels of inhibitory CD158a/b along with decreased expression of activating NKG2D and CD161 and increased inhibitory NKG2A levels. Patient NK cell cytotoxic activity was impaired, as were their degranulation and inflammatory cytokine production, which partially recovered following non-receptor-dependant stimulation.The phenotypically skewed and restricted population of patient NK cells, along with their blunted cytotoxic and immune-regulatory activity, appear to be driven by exposure to lymphoma environment. These NK cell functional aberrations could support lymphoma immune evasion and should be considered in the era of cellular therapy.