Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment

作者：Richard Pelzl, Giulia Benintende, Franziska Gsottberger, Julia Katharina Scholz, Matthias Ruebner, Hao Yao, Kerstin Wendland, Kai Rejeski, Heidi Altmann, Srdjan Petkovic, Lisa Mellenthin, Sabrina Kübel, Moritz Schmiedeberg, Paulina Klein, Agnese Petrera, Rebecca Baur, Sophie Eckstein, Sandra Hoepffner-Grundy, Christoph Röllig, Marion Subklewe, Hanna Huebner, G. Schett, Andréas Mackensen, Luca Laurenti, Frederik Graw, Simon Völkl, Krystelle Nganou‐Makamdop, Fabian Müller · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024027877 · 被引用次数：8 · 研究领域：Immune Cell Function and Interaction、Lymphoma Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers

ABSTRACT: Immunotherapy has become standard of care in the treatment of diffuse large B-cell lymphoma (DLBCL). Changes in immunophenotypes observed at first diagnosis predict therapy outcome but little is known about the resolution of these alterations in remission. Comprehensive characterization of immune changes from fresh, peripheral whole blood revealed a functionally relevant increase of myeloid-derived suppressor cells, reduced naïve T cells, and an increase of activated and terminally differentiated T cells before treatment, which aggravated after therapy. Suggesting causal relation, injection of lymphoma in mice induced similar changes in the murine T cells. Distinct immune imprints were found in those who have survived breast cancer and acute myeloid leukemia. Identified alterations persisted beyond 5 years of ongoing complete remission and correlated with increased proinflammatory markers such as interleukin-6, β2-microglobulin, or soluble CD14 in DLBCL. The chronic inflammation was associated with functionally blunted T-cell immunity against severe acute respiratory syndrome coronavirus 2-specific peptides, and reduced responses correlated with reduced naïve T cells. Persisting inflammation was confirmed by deep sequencing and by cytokine profiles, together pointing toward a compensatory activation of innate immunity. The persisting, lymphoma-induced immune alterations in remission may explain long-term complications, have implications for vaccine strategies, and a...