Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model

• Published in: Communications biology Vol. 6; no. 1; p. 444
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 631/250/1619; 631/250/580; 631/61/17; Animals; B-cell lymphoma; Biology; Biomedical and Life Sciences; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell activation; Cloning; Cross-protection; Humans; Immune system; Immunodeficiency; Immunological memory; Jurkat Cells; Life Sciences; Lymphocytes; Lymphocytes T; Lymphoma; Lymphoma, B-Cell - metabolism; Memory cells; Mice; Receptors, Antigen, T-Cell - metabolism; T cell receptors; Tumor cells; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-04824-z

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.