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Accession PRJNA924727
Title Human CD4 cytotoxic T lymphocytes mediate potent tumor control via tumor cell HLA 2 class II expression in a humanized immune system mouse model
Relevance Unknown
Data types Transcriptome or Gene expression
Sample scope Multispecies
Description 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.
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Organization Regeneron Pharmaceuticals, Inc
Data Source NCBI

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Experiment (22)  show -