American Association for Cancer Research
Browse

Figure S7 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development

Download (398.45 kB)
journal contribution
posted on 2024-04-01, 07:24 authored by Lior Goldberg, Eric R. Haas, Ryan Urak, Vibhuti Vyas, Khyatiben V. Pathak, Krystine Garcia-Mansfield, Patrick Pirrotte, Jyotsana Singhal, James L. Figarola, Ibrahim Aldoss, Stephen J. Forman, Xiuli Wang

Figure S7. Growth curve of CAR T cells produced in RPMI or CSF; n = 7 patients.

Funding

National Institutes of Health (NIH)

History

ARTICLE ABSTRACT

Metabolic reprogramming is a hallmark of T-cell activation, and metabolic fitness is fundamental for T-cell–mediated antitumor immunity. Insights into the metabolic plasticity of chimeric antigen receptor (CAR) T cells in patients could help identify approaches to improve their efficacy in treating cancer. Here, we investigated the spatiotemporal immunometabolic adaptation of CD19-targeted CAR T cells using clinical samples from CAR T-cell–treated patients. Context-dependent immunometabolic adaptation of CAR T cells demonstrated the link between their metabolism, activation, differentiation, function, and local microenvironment. Specifically, compared with the peripheral blood, low lipid availability, high IL15, and low TGFβ in the central nervous system microenvironment promoted immunometabolic adaptation of CAR T cells, including upregulation of a lipolytic signature and memory properties. Pharmacologic inhibition of lipolysis in cerebrospinal fluid led to decreased CAR T-cell survival. Furthermore, manufacturing CAR T cells in cerebrospinal fluid enhanced their metabolic fitness and antileukemic activity. Overall, this study elucidates spatiotemporal immunometabolic rewiring of CAR T cells in patients and demonstrates that these adaptations can be exploited to maximize the therapeutic efficacy of CAR T cells. The spatiotemporal immunometabolic landscape of CD19-targeted CAR T cells from patients reveals metabolic adaptations in specific microenvironments that can be exploited to maximize the therapeutic efficacy of CAR T cells.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC