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. Analysis of regressing Raji tumor indicated human T cell infiltration. We isolated T cells from regressing Raji tumors as well as concomitant spleens to assess the transcriptional profile of T cells as well as specific TCR sequences that may be expanded in infiltrating T cells. Overall design: We isolated human T cells from regressing Raji tumors, outgrowing (uncontrolled) Raji tumors as well as concomitant spleens. Additional controls were T cells isolated from non-tumor challenged HIS mice spleens. T cells were isolated by FACS sorting for hCD45+/mCD45- and CD3+/CD19- cells from prepared tissues. We performed high throughput transcriptomic (scRNAseq) and TCR repertoire (scTCRseq) characterization of isolated human T cells.