项目编号

PRJNA924727

项目标题

Human CD4 cytotoxic T lymphocytes mediate potent tumor control via tumor cell HLA 2 class II expression in a humanized immune system mouse model

涉及领域

Unknown

数据类型

Transcriptome or Gene expression

样品范围

Multispecies

描述信息

Efficacy of immune checkpoint inhibitors in cancer can be limited by dysfunction of CD8 T cells or down-regulation of HLA class I. Tumor control mechanisms independent of the CD8/HLA-I axis would bypass these limitations. CD4 cytotoxic T lymphocytes (CTLs) have been detected in diverse human cancers. However, their independent roles in tumor immunity are underexplored. Here, we report CD4 T cell-dependent spontaneous tumor regression and subsequent memory responses in a humanized immune system (HIS) mouse model. HT-29 tumors, which upregulate HLA class II expression in response to IFN-γ, regressed or were eliminated in a subset of tumor implanted HIS mice. Mice with regressing tumors showed increased cytotoxic CD4 T cells in blood and tumors and enhanced HLA-II expression on tumor cells compared to mice with progressing tumors. The intratumoral CD4 T cell subset associated with tumor regression expressed multiple cytotoxic markers and exhibited clonal expansion. Notably, tumor control was abrogated by depletion of CD4 but not CD8 T cells. CD4 T cells derived from tumor-regressing mice exhibited HLA-II-dependent and tumor cell-specific killing ex vivo. Taken together, our study demonstrates a critical role of human CD4 CTLs in mediating potent tumor control independent of CD8 T cells and provides a novel platform to study human CD4 CTL-mediated anti-tumor immunity. Overall design: Data includes untreated same donor-engrafted StRG47 HIS mice implanted with HT-29 colon tumor. Tumor samples were collected after 1 month and sorted human CD45+ and mouse CD45+ for sequencing. There are 11 samples in total, 5 StRG47 HIS regressors and 6 StRG47 HIS progressors. The single cell data is aligned to both the human and mouse genome and the TCR data is aligned to human.

项目相关网站链接

网站信息描述

发布日期

2023-04-25

提交单位

Regeneron Pharmaceuticals, Inc

数据来源

NCBI

项目包含数据信息

资源名称	描述
Experiment (22) show	-
SRX19050177	GSM6938387: StRG47-Prog-hCD45-2 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050178	GSM6938388: StRG47-Prog-hCD45-2 (TCR-seq); Mus musculus; RNA-Seq
SRX19050182	GSM6938392: StRG47-Prog-hCD45-4 (TCR-seq); Mus musculus; RNA-Seq
SRX19050175	GSM6938385: StRG47-Prog-hCD45-1 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050184	GSM6938394: StRG47-Prog-hCD45-5 (TCR-seq); Mus musculus; RNA-Seq
SRX19050181	GSM6938391: StRG47-Prog-hCD45-4 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050183	GSM6938393: StRG47-Prog-hCD45-5 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050187	GSM6938397: StRG47-Reg-hCD45-1 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050180	GSM6938390: StRG47-Prog-hCD45-3 (TCR-seq); Mus musculus; RNA-Seq
SRX19050189	GSM6938399: StRG47-Reg-hCD45-2 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050186	GSM6938396: StRG47-Prog-hCD45-6 (TCR-seq); Mus musculus; RNA-Seq
SRX19050188	GSM6938398: StRG47-Reg-hCD45-1 (TCR-seq); Mus musculus; RNA-Seq
SRX19050192	GSM6938402: StRG47-Reg-hCD45-3 (TCR-seq); Mus musculus; RNA-Seq
SRX19050185	GSM6938395: StRG47-Prog-hCD45-6 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050194	GSM6938404: StRG47-Reg-hCD45-4 (TCR-seq); Mus musculus; RNA-Seq
SRX19050191	GSM6938401: StRG47-Reg-hCD45-3 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050193	GSM6938403: StRG47-Reg-hCD45-4 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050190	GSM6938400: StRG47-Reg-hCD45-2 (TCR-seq); Mus musculus; RNA-Seq
SRX19050196	GSM6938406: StRG47-Reg-hCD45-5 (TCR-seq); Mus musculus; RNA-Seq
SRX19050195	GSM6938405: StRG47-Reg-hCD45-5 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq
SRX19050176	GSM6938386: StRG47-Prog-hCD45-1 (TCR-seq); Mus musculus; RNA-Seq
SRX19050179	GSM6938389: StRG47-Prog-hCD45-3 (scRNA-seq); Homo sapiens; Mus musculus; RNA-Seq