2024-05-28 ヒューストン大学(UH)
◆研究チームは、TIMINGというAIを用いた新しい技術を使い、個々のT細胞と腫瘍細胞の相互作用を追跡し、単一細胞RNAシーケンシングデータと統合しました。その結果、CD8-fit T細胞が高い運動性と連続殺傷能力を持つことを発見し、これが長期的な臨床応答と関連していることが分かりました。この発見は、他の腫瘍にも応用可能で、将来のT細胞療法の効果向上に貢献する可能性があります。研究成果はNature Cancer誌に掲載されています。
<関連情報>
- https://uh.edu/news-events/stories/2024/may/05282024-tcells-discovered-lymphoma-varadarjan.php
- https://www.nature.com/articles/s43018-024-00768-3
動的多次元単一細胞プロファイリングによるびまん性大細胞型B細胞リンパ腫における臨床的に有効なCAR T細胞サブセットの同定 Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling
Ali Rezvan,Gabrielle Romain,Mohsen Fathi,Darren Heeke,Melisa Martinez-Paniagua,Xingyue An,Irfan N. Bandey,Melisa J. Montalvo,Jay R. T. Adolacion,Arash Saeedi,Fatemeh Sadeghi,Kristen Fousek,Nahum Puebla-Osorio,Laurence J. N. Cooper,Chantale Bernatchez,Harjeet Singh,Nabil Ahmed,Mike Mattie,Adrian Bot,Sattva Neelapu & Navin Varadarajan
Science Cancer Published:15 May 2024
DOI:https://doi.org/10.1038/s43018-024-00768-3
An Author Correction to this article was published on 22 May 2024
Abstract
Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8+ T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes. Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses in individuals treated with axicabtagene ciloleucel, (2) longitudinally persist in individuals after treatment with CAR T cells and (3) are tumor migrating cytolytic cells capable of intratumoral expansion in solid tumors. Our results demonstrate the power of multimodal integration of single-cell functional assessments for the discovery and application of CD8-fit T cells as a T cell subset with optimal fitness in cell therapy.
