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

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.

Automated summary

Immunodeficient mice reconstituted with a human immune system (HIS mice) are a valuable tool for studying human immune responses to tumors. However, these mice often exhibit sub-optimal immune responses and lack antigen-specific B or T cell memory. In this study, we observed spontaneous regression of human B cell lymphoma Raji in HIS mice. Tumor regression was dependent on CD4+ and CD8+ T cells and resulted in T cell memory. We also found clonal expansion of specific T cell receptors (TCRs) and Raji-specific T cell reactivity in regressing tumors.