anaylsis of the immunophenotype and functional immune impairment in DLBCL survivors. Large B-cell lymphoma imprints dysfunctional immune phenotype that persists years after treatment

Immunotherapy has become standard of care in the treatment of diffuse large B-cell lymphoma (DLBCL). Despite distinct immunophenotypes predicting outcome, little is known about persisting immune alterations after treatment. We thus comprehensively characterized immune changes throughout the course of DLBCL. Fresh whole blood analyses revealed a functionally relevant increase of myeloid-derived suppressor cells, a reduction of naïve T-cells, and an increase of activated and terminally differentiated T-cells already before treatment and aggravated after therapy. Suggesting causal relation, injection of lymphoma in mice induced similar T-cell changes. The alterations persisted beyond five years in remission and correlated with increased pro-inflammatory markers including IL-6, B2M and sCD14. The chronic inflammation impaired adaptive immune responses against SARS-CoV-2 and was confirmed by deep sequencing and cytokine profiles, pointing towards activated innate immunity. These substantial, lymphoma-induced immune alterations may explain long-term complications of lymphoma survivors and may correlate with efficacy of immunotherapy.