Children treated against lymphoid malignancies display diminished IFN-gamma producing T cells after polyclonal and Varicella zoster virus peptide activation

Abstract Knowledge on the impact of hematological cancers and their treatment on children's memory T cells is limited. Memory T cells play a crucial role in defending against herpesviruses, particularly relevant in pediatric cancer care. We examined 40 children undergoing cancer or hematological disorder treatment and 13 healthy controls, focusing on memory T-cell subsets using flow cytometry and analyzed cytokine-secreting T cells in response to polyclonal and varicella-zoster virus (VZV) peptides. Children with lymphoid malignancies or post-allo-HSCT showed an accumulation of CD4 + T effector memory (TEM)/ T effector (TEFF) cells among CD3 + cells as follows; [51% (3.8–68.8%)] versus 5.5% (1.3–40.4%), p < 0.001]. Similarly, CD8 + TEM/TEFF proportions were elevated in patients treated for lymphoid malignancies. Following VZV stimulation, these children displayed a significantly lower number of cytokine-secreting cells (183 (30–3181) vs 47 (9–368), p < 0.05) compared to children with other cancer diagnosis/healthy controls. The former group also exhibited a diminished IFN-γ response upon VZV stimulation compared to healthy controls [2 (0–308) vs 53 (5–351), p < 0.001] also noted after polyclonal stimulation. This suggests qualitative differences in T-cell memory among children treated for lymphoid cancers, potentially increasing their susceptibility to severe viral infections, and impacting immunotherapy.