Studying the impact of lysosomal drugs on cytokine secretion and lysosomal integrity in B cell lymphoma models -focusing on the translational significance

Abstract

Suppressing the abnormal activity of lysosomes in cancer outgrowth could revolutionize treatment, though they have yet to be established as direct therapeutic targets in cancer treatment. Cytokines secreted by B lymphoma cells may indicate drug response, serving as prognostic markers for disease monitoring. This study investigates the translational potential of lysosome -targeting drugs by evaluating correlations between cytokine secretion and malignant growth in B cell lymphoma spheroids and patient-derived organoids during 2 week drug exposure. We hypothesized that drugs reducing malignant growth would also lower cytokine levels. B cell lymphoma cultures were treated with two potent compounds, penfluridol and ebastine, with DMSO as control. TNF-α cytokine levels were measured from patient-derived organoids and diffuse large B cell lymphoma (DLBCL) cell line spheroids using a sandwich ELISA method. Live cell monitoring monitored lymphoma organoid outgrowth during 2 weeks, while immunofluorescence image analysis of 2D and 3D cultures assessed drug effects on lysosome size and morphology. Results showed a correlation between lowered cytokine TNF-α level and reduced malignant growth upon employing lysosome-targeting drugs penfluridol and ebastine. Immunofluorescent imaging demonstrated that these drugs also effectively disrupt lysosomal integrity within the treated cells. Our findings suggest cytokine screenings could optimize therapeutic strategies for B cell lymphoma patients, although further research on cytokine regulation remains essential.