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- Title
Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model.
- Authors
Patel, A. K.; Dhanik, Ankur; Lim, Wei Keat; Adler, Christina; Ni, Min; Wei, Yi; Zhong, Maggie; Nguyen, Cindy; Zhong, Jun; Lu, Yi-Fen; Thurston, Gavin; Macdonald, Lynn; Murphy, Andrew; Gurer, Cagan; Frleta, Davor
- Abstract
Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice. Raji tumor spontaneously regresses via human T cell-mediated tumor control in human immune system-reconstituted mice.
- Subjects
T cells; SPONTANEOUS cancer regression; IMMUNE system; IMMUNOLOGIC memory; B cell lymphoma; LABORATORY mice; T cell receptors
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-04824-z