Authors
Jia-Jye Lee, Peirong Hu, Kun Luo, Jinling Wang, Emily Neil, Dongju Park, Robert Pinard, Yazeed Sawalha, Nathan Denlinger, Evandro Bezerra, Pradyot Dash, Dina Schneider, Ashley Krull, Lynn Odonnell, Lapo Alinari, Wing Keung Chan, Dan Jones, Rimas J Orentas, Marcos de Lima, Sumithira Vasu
Published in
iScience. Volume 29. Issue 8. Pages 116847. Aug 21, 2026. Epub Jul 17, 2026.
Abstract
CD19-directed chimeric antigen receptor (CAR)-engineered T cells have transformed cellular therapy for hematologic malignancies but have also raised concerns about secondary malignancies. A spatial profiling method was used to analyze the tumor microenvironment and define native and CAR T cell association with a pleomorphic sarcoma arising 12 months post-CAR T therapy for B cell lymphoma. Although CAR T sequences were absent in the secondary tumor, our approach enabled profiling of the stroma, tumor, and infiltrating T cells. Spatial analysis incorporated proteomics via serial antibody staining and transcriptomics using RNA hybridization on an automated MACSima imaging cyclic staining (MICS) system, which allows for in situ detection of CAR T cells. We report here the prevalence of CAR-positive T cells in patient-derived tissue sections, observed metabolic and proliferative shifts in the tumor and its microenvironment, and immune checkpoint analysis. These findings provide insights into post-CAR T secondary cancers and highlight tools that may guide future targeted therapies.
PMID:
42502392
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.
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