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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 08, 2018 |
| Title |
The expression of MHC class II molecules on murine breast tumors delays T cell exhaustion, expands the T cell repertoire and slows tumor growth |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
Transfection with the human class II transcriptional activator (hCIITA) promotes MHCII expression on TS/A breast cancer cells. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4+ and CD8+ T cells. Additionally, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8+ T cells in tumors depended on CD4+ T cells. However, both CD4+ and CD8+ T cells eventually became exhausted, even in MHCII-expressing tumors. Treatment with anti-CTLA4, but not anti-PD-1 or anti-TIM-3, promoted complete eradication of MHCII-expressing tumors. These results suggest tumor cell expression of MHCII facilitates the local activation of CD4+ T cells, indirectly helps the activation and expansion of CD8+ T cells and, in combination with the appropriate checkpoint inhibitor, promotes tumor regression.
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| Overall design |
To test whether local MHCII expression promoted T cell clonal expansion or accumulation, we harvested 12 control and 12 MHCII-expressing whole tumor samples and sequenced the CDR3 region of the TCRbeta chain to identify unique T cell clones.
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| Contributor(s) |
McCaw TR, Li M, Starenki D, Cooper SJ, Liu M, Meza-Perez S, Arend RC, Buchsbaum DJ, Forero A, Randall TD |
| Citation(s) |
30334128, 30485278 |
| Submission date |
Sep 07, 2018 |
| Last update date |
Jan 27, 2019 |
| Contact name |
Dmytro Starenki |
| E-mail(s) |
dstarenki@hudsonalpha.org
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| Phone |
2563275265
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| Organization name |
HudsonAlpha Institute for Biotechnology
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| Street address |
601 Genome Way
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| City |
Huntsville |
| State/province |
Alabama |
| ZIP/Postal code |
35806 |
| Country |
USA |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA489881 |
| SRA |
SRP160388 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119670_RAW.tar |
6.5 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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