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Postinfusion PD-1+ CD8+ CAR T cells identify patients responsive to CD19 CAR T-cell therapy in non-Hodgkin lymphoma.
- Source :
-
Blood advances [Blood Adv] 2024 Jun 25; Vol. 8 (12), pp. 3140-3153. - Publication Year :
- 2024
-
Abstract
- Abstract: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Robust biomarkers and a complete understanding of CAR T-cell function in the postinfusion phase remain limited. Here, we used a 37-color spectral flow cytometry panel to perform high dimensional single-cell analysis of postinfusion samples in 26 patients treated with CD28 costimulatory domain containing commercial CAR T cells for NHL and focused on computationally gated CD8+ CAR T cells. We found that the presence of postinfusion Programmed cell death protein 1 (PD-1)+ CD8+ CAR T cells at the day 14 time point highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR T cells, including PD-1+ T cell factor 1 (TCF1)+ stem-like CAR T cells and PD-1+ T-cell immunoglobulin and mucin-domain containing-3 (TIM3)+ effector-like CAR T cells that correlated with improved clinical outcomes such as response and progression-free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here, we identified robust biomarkers of response to CD28 CAR T cells and highlight the importance of PD-1 positivity in CD8+ CAR T cells after infusion in achieving CR.<br /> (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Subjects :
- Humans
Male
Female
Middle Aged
Aged
Adult
Antigens, CD19 immunology
Receptors, Chimeric Antigen metabolism
Receptors, Chimeric Antigen immunology
Treatment Outcome
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Lymphoma, Non-Hodgkin therapy
Lymphoma, Non-Hodgkin immunology
Programmed Cell Death 1 Receptor metabolism
Immunotherapy, Adoptive methods
Subjects
Details
- Language :
- English
- ISSN :
- 2473-9537
- Volume :
- 8
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Blood advances
- Publication Type :
- Academic Journal
- Accession number :
- 38607381
- Full Text :
- https://doi.org/10.1182/bloodadvances.2023012073