Year: 2026
Type: article
Abstract: Introduction Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of relapsed or refractory B-cell malignancies. Beyond its antitumor activity, CAR-T therapy induces dynamic changes across multiple immune compartments. We characterized longitudinal immune remodeling by integrating CAR-T cells, endogenous T cells, NK cells, B cells, and monocytes. Methods Peripheral blood samples from patients receiving anti-CD19 CAR-T therapy (CAAE: 65750722.3.0000.5432) were prospectively collected before infusion and during follow-up. Peripheral blood mononuclear cells were analyzed by multiparameter flow cytometry using antibody panels including CD45, CD3, CD4, CD8, anti-CD19 CAR, CD56, CD16, CD69, CD62L, CD45RO, TIGIT, CD19, CD14, CD25, CD127, and HLA-DR. Results Immune profiling demonstrated multicompartment remodeling following anti-CD19 CAR-T therapy. CAR-positive T-cell expansion varied markedly among patients and was accompanied by redistribution of endogenous CD4⁺ and CD8⁺ T-cell subsets, including changes in naïve, central memory, effector memory, and terminal effector populations, together with modulation of PD-1, LAG-3, and CD38 expression. NK cells also displayed phenotypic remodeling, including changes in CD56⁺CD16⁺ populations and immune checkpoint expression. B-cell depletion remained consistent with on-target anti-CD19 activity. Monocyte frequencies and HLA-DR expression were dynamically remodeled throughout the follow-up period, indicating changes in antigen-presenting compartments. Overall, immune remodeling extended beyond the infused CAR-T product and simultaneously involved adaptive, innate, humoral, and myeloid compartments. Discussion These findings support coordinated immune remodeling. Expansion of CAR-T cells occurred alongside redistribution of endogenous T-cell subsets, NK-cell remodeling, B-cell aplasia, and modulation of monocyte antigen-presentation markers, suggesting systemic immune reorganization. This coordinated remodeling may provide a biological framework for understanding post-treatment immune competence and should be investigated in larger longitudinal cohorts including clinical outcomes, infectious complications, and CAR-T persistence. Conclusion Associated with multicompartment immune remodeling involving adaptive, innate, humoral, and myeloid compartments. These exploratory findings support further longitudinal studies to investigate multicompartment immune remodeling in relation to clinical outcomes, infectious complications, and CAR-T persistence.
Authors: Ana Luiza Sionti PACHECO, Arianne Fagotti GUSMÃO, Larissa Campos SOUZA, Vanessa Dos Anjos BOVOLENTA, Ana Costa CORDEIRO, Bianca Batista CAL, Gabriel ANDRADE DE PAULA, Filipe Freires DOS SANTOS, Raquel Garcia DA SILVA, Mariana Soares GOMES, Alexandre Silva CHAVES, Daniela DELECHIAVE, Sabrina Pinho Costa MENDES, Lais Lie SENDA, Marina Mattos NASCIMENTO, Mariela Pires CABRAL PICCIN, Tiago Da Silva MEDINA, Jayr SCHMIDT FILHO, Marjorie Vieira BATISTA
Institution: AC Camargo Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223153056