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| Status |
Public on May 11, 2023 |
| Title |
Bulk TCRseq analysis on CD8+ T cells in FSCN1-KI bone marrow chimera mice following anti-CD4 and anti-PDL1 mAb treatment |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
The repertoire of tumor-infiltrating T cells is a novel perspective to characterize effective anti-tumor T cell responses. Previous studies reported that the oligoclonal expansion in tumor T-cell repertoire is associated with anti-tumor effects. However, the contribution of the expansion of diverse T-cell clones remained unclear. We demonstrated that the polyclonal fraction of tumor-reactive T-cell repertoire consisting of relatively minor clones, increased in tumor-bearing mice treated with anti-PD-L1 or anti-CD4 monoclonal antibodies (mAbs), while the oligoclonal fraction consisting of major clones was unchanged. Moreover, the polyclonal fraction was enriched with progenitor exhausted T cells, essential for a durable anti-tumor response, and more dependent on CCR7+ migratory dendritic cells, responsible for priming tumor-reactive T cells in the tumor-draining lymph node (dLN). These results proposed that the expansion of diverse tumor-reactive clones, “clonal spreading,” is an important mechanism by which anti-PD-L1 and anti-CD4 treatments exert robust and durable anti-tumor T-cell responses.
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| Overall design |
CD8+ T cells from tumor, and CD8+ CD44high T cells from draining lymph node (dLN) were collected from B16F10 tumor-bearing Fscn1 knock-in BMC mice treated with anti-CD4 monoclonal antibody (mAb), anti-PD-L1 mAb or combination of anti-CD4 and anti-PD-L1 mAbs, with or without diphtheria toxin (DT) administration. Bulk TCR sequencing was performed, and T cell clones that overlap between tumor and dLN were identified.
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| Contributor(s) |
Aoki H, Tsunoda M, Ogiwara H, Shimizu H, Abe H, Abe T, Shichino S, Matsushima K, Ueha S |
| Citation(s) |
36988477 |
| |
| Submission date |
Mar 09, 2022 |
| Last update date |
May 12, 2023 |
| Contact name |
Hiroyasu Aoki |
| E-mail(s) |
haoki-tky@rs.tus.ac.jp
|
| Phone |
08013746493
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| Organization name |
Tokyo University of Science
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| Department |
Research Institute for Biomedical Sciences
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| Lab |
Division of Molecular Regulation of Inflammatory and Immune Diseases
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| Street address |
2669 Yamazaki
|
| City |
Noda |
| State/province |
Chiba |
| ZIP/Postal code |
278-0022 |
| Country |
Japan |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (54)
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| This SubSeries is part of SuperSeries: |
| GSE198211 |
Clonal spreading of tumor-infiltrating T cells underlies the durable antitumor effects of PD-1 blockade and anti-CD4 monoclonal antibody |
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| Relations |
| BioProject |
PRJNA814225 |
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