免疫缺陷小鼠再植入人类免疫系统（HIS小鼠）能产生人类T细胞，这使它们成为研究肿瘤对人类免疫反应的吸引人的系统。然而，此类HIS小鼠通常表现出亚优性的免疫挑战反应以及未能发展特异性抗原的B或T细胞记忆。本文报告HIS小鼠介导人源性B淋巴瘤Raji的自发消退。肿瘤消退依赖于CD4+和CD8+T细胞反应，结果是T细胞记忆。激发的T细胞记忆主要是Raji特异性的，然而也激发了对相关的B淋巴瘤细胞系Ramos的某种水平的交叉保护。单细胞RNA测序分析表明，在消退Raji肿瘤中激活了CD8+ T细胞，以及特定T细胞受体（TCR）的克隆扩增。从Raji浸润的T细胞中克隆出TCR并移植到Jurkat报告细胞系中，表明具有针对Raji肿瘤细胞的特异性反应。总的来说，我们报告了一个研究HIS小鼠中体内人类T细胞肿瘤免疫的平台，通过强调自发Raji肿瘤消退、克隆TCR扩张和T细胞记忆。©2023年作者。

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.© 2023. The Author(s).