Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia

作者：Anna Guarini, Giulia Radice, Nadia Peragine, Chiara Buracchi, Maria Stefania De Propris, Alice Di Rocco, Arianna Di Rocco, Sabina Chiaretti, Alex Moretti, Sara Napolitano, Maurizio Martelli, Adriana Balduzzi, Giuseppe Gaipa, Andrea Biondi, Robin Foà · 发表于：Cancers · 年份：2023 · DOI：10.3390/cancers15092411 · 被引用次数：8 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Viral Infectious Diseases and Gene Expression in Insects

Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults.