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GEO help: Mouse over screen elements for information. |
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Status |
Public on Feb 02, 2023 |
Title |
Targeting tumor cells toward the antigenic specificity of bystander T cells in tumor microenvironment potentiates cancer immunotherapy |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in tumor microenvironment (TME), leading to the inefficacious immunotherapies in most cancer patients. In contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in TME. To leverage TBYS cells in TME to eradicate tumor cells, we developed an oncolytic virus-based immunotherapy that delivers TBYS cell epitopes (OV-BYTE) into tumor cells, which efficiently redirects the antigen specificity of tumor cells to preexisting TBYS cells and effectively retards tumor growth in multiple preclinical models. Remarkably, the OV-BYTE strategy curtailed tumor progression by targeting SARS-CoV-2-specific T cell memory induced by natural infection or vaccination, providing important insights into the improvement of cancer immunotherapies in a great population with a history of SARS-CoV-2 infection or COVID-19 vaccination.
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Overall design |
To explore the molecular features of TBYS cells and how these cells respond to OV-BYTE therapy, C57BL/6 mice receving the transfer of congenically marked P14 CD8+ and SM CD4+ T cells recognizing two distinct LCMV glycoprotein (GP) epitopes were infected with LCMV Armstrong and engrafted with MC38 cells on day 60-post infection when LCMV immune memory was established. After 5 injections of PBS or NDV-WT or NDV-GP, MC38 tumor-infiltrating bystander P14 CD8+ and SM CD4+ T cells were FACS-sorted and analyzed using scRNA-seq. As controls, conventional memory SM CD4+ T cells were harvested from the spleens of C57BL/6 mice at day 60-post infection of LCMV Armstrong. To explore the changes of TCR repertoire in tumor-reactive CD8+ T cells, LCMV Armstrong-infected mice were engrafted with MC38 tumors and then intratumorally administrated with PBS or NDV-WT or NDV-GP. Then, CD45+ immune cells and CD45- non-immune cells from PBS- or NDV-WT- or NDV-GP-treated MC38 tumors were isolated and performed with scRNA-seq/scTCR-seq library construction. Furthermore, MC38 tumor-specific p15E tetramer+ CD8+ T cells were also isolated from PBS- or NDV-WT- or NDV-GP-treated MC38 tumors and performed with TCR-seq libarary construction.
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Contributor(s) |
Chen X, Li Z |
Citation(s) |
- Chen X, Zhao J, Yue S, Li Z et al. An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy. Nat Cancer 2024 Jul;5(7):1063-1081. PMID: 38609488
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Submission date |
Jan 02, 2023 |
Last update date |
Aug 26, 2024 |
Contact name |
Ziyu Li |
E-mail(s) |
2101110522@stu.pku.edu.cn
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Phone |
86-18631227988
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Organization name |
Peking University
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Department |
Biomedical Pioneering Innovation Center
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Lab |
Fan Bai lab
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Street address |
5 Summer Palace Road, Haidian District, Beijing, China
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City |
Beijing |
ZIP/Postal code |
100871 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (13)
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GSM6911493 |
D60,scRNAseq |
GSM7843393 |
Sample 1_p15E+CD8+ T cell, PBS, TCR-seq |
GSM7843394 |
Sample 2_p15E+CD8+ T cell, NDV-WT, TCR-seq |
GSM7843395 |
Sample 3_p15E+CD8+ T cell, NDV-GP, TCR-seq |
GSM7843396 |
Sample 4_CD45+ immune cells and CD45- non-immune cells, PBS, scRNA-seq |
GSM7843397 |
Sample 5_CD45+ immune cells and CD45- non-immune cells, NDV-WT, scRNA-seq |
GSM7843398 |
Sample 6_CD45+ immune cells and CD45- non-immune cells, NDV-GP, scRNA-seq |
GSM7843399 |
Sample 7_CD45+ immune cells and CD45- non-immune cells, PBS, scTCR-seq |
GSM7843400 |
Sample 8_CD45+ immune cells and CD45- non-immune cells, NDV-WT, scTCR-seq |
GSM7843401 |
Sample 9_CD45+ immune cells and CD45- non-immune cells, NDV-GP, scTCR-seq |
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Relations |
BioProject |
PRJNA917440 |
Supplementary file |
Size |
Download |
File type/resource |
GSE222002_RAW.tar |
667.7 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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