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Updated: Jan 27, 2026
Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo
Published on: July 25, 2025
Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity
Marine Cazaux1,2, Capucine L Grandjean1, Fabrice Lemaître1
1Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France.
Abstract:
CAR T cells represent a potentially curative strategy for B cell malignancies. However, the outcome and dynamics of CAR T cell interactions in distinct anatomical sites are poorly understood. Using intravital imaging, we tracked interactions established by anti-CD19 CAR T cells in B cell lymphoma-bearing mice. Circulating targets trapped CAR T cells in the lungs, reducing their access to lymphoid organs. In the bone marrow, tumor apoptosis was largely due to CAR T cells that engaged, killed, and detached from their targets within 25 min. Notably, not all CAR T cell contacts elicited calcium signaling or killing while interacting with tumors, uncovering extensive functional heterogeneity. Mathematical modeling revealed that direct killing was sufficient for tumor regression. Finally, antigen-loss variants emerged in the bone marrow, but not in lymph nodes, where CAR T cell cytotoxic activity was reduced. Our results identify a previously unappreciated level of diversity in the outcomes of CAR T cell interactions in vivo, with important clinical implications.
Insights
CAR T cell therapy shows promise for B cell cancers. This study reveals diverse CAR T cell interactions and functional heterogeneity in vivo, impacting treatment effectiveness and antigen-loss variant emergence.
Area of Science:
- Immunology
- Oncology
- Cellular Biology
Background:
- Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for B cell malignancies.
- Understanding CAR T cell dynamics at different anatomical sites is crucial for optimizing therapy.
Purpose of the Study:
- To investigate the in vivo interactions of anti-CD19 CAR T cells with B cell lymphoma.
- To explore the impact of anatomical location on CAR T cell efficacy and tumor response.
Main Methods:
- Intravital imaging was used to track CAR T cell interactions in lymphoma-bearing mice.
- Mathematical modeling was employed to analyze CAR T cell killing efficiency.
- Analysis of antigen-loss variant emergence in different anatomical sites.
Main Results:
- CAR T cells were trapped in the lungs, limiting access to lymphoid organs.
- Rapid CAR T cell-mediated tumor apoptosis was observed in the bone marrow.
- Significant functional heterogeneity in CAR T cell-tumor interactions was identified.
- Antigen-loss variants emerged in the bone marrow but not in lymph nodes.
Conclusions:
- CAR T cell interactions exhibit extensive functional diversity in vivo.
- Direct CAR T cell killing is sufficient for tumor regression.
- Anatomical site influences CAR T cell efficacy and the development of resistance mechanisms.
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