COORDINATED IMMUNE ECOSYSTEM REMODELING FOLLOWING ANTI-CD19 CAR-T CELL THERAPY
- 1A.C. Camargo Cancer Center, São Paulo, SP, Brazil
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.
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BibTeX
@article{pacheco2026coordinated,
title = {{COORDINATED IMMUNE ECOSYSTEM REMODELING FOLLOWING ANTI-CD19 CAR-T CELL THERAPY}},
author = {Ana Luiza Sionti PACHECO and Arianne Fagotti GUSMÃO and Larissa Campos SOUZA and Vanessa Dos Anjos BOVOLENTA and Ana Costa CORDEIRO and Bianca Batista CAL and Gabriel ANDRADE DE PAULA and Filipe Freires DOS SANTOS and Raquel Garcia DA SILVA and Mariana Soares GOMES and Alexandre Silva CHAVES and Daniela DELECHIAVE and Sabrina Pinho Costa MENDES and Lais Lie SENDA and Marina Mattos NASCIMENTO and Mariela Pires CABRAL PICCIN and Tiago Da Silva MEDINA and Jayr SCHMIDT FILHO and Marjorie Vieira BATISTA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106844},
url = {https://doi.org/10.1016/j.htct.2026.106844},
note = {CC BY},
}
RIS
TY - JOUR
TI - COORDINATED IMMUNE ECOSYSTEM REMODELING FOLLOWING ANTI-CD19 CAR-T CELL THERAPY
AU - Ana Luiza Sionti PACHECO
AU - Arianne Fagotti GUSMÃO
AU - Larissa Campos SOUZA
AU - Vanessa Dos Anjos BOVOLENTA
AU - Ana Costa CORDEIRO
AU - Bianca Batista CAL
AU - Gabriel ANDRADE DE PAULA
AU - Filipe Freires DOS SANTOS
AU - Raquel Garcia DA SILVA
AU - Mariana Soares GOMES
AU - Alexandre Silva CHAVES
AU - Daniela DELECHIAVE
AU - Sabrina Pinho Costa MENDES
AU - Lais Lie SENDA
AU - Marina Mattos NASCIMENTO
AU - Mariela Pires CABRAL PICCIN
AU - Tiago Da Silva MEDINA
AU - Jayr SCHMIDT FILHO
AU - Marjorie Vieira BATISTA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106844
UR - https://doi.org/10.1016/j.htct.2026.106844
AB - 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.
SN - 2531-1379
SN - 2531-1387
ER -