Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model.
Commun Biol
; 6(1): 444, 2023 04 22.
Article
em En
| MEDLINE
| ID: mdl-37087494
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
/
Linfócitos T CD8-Positivos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos