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| Status |
Public on Nov 28, 2018 |
| Title |
Extrinsic C5a Activation Regulates Squamous Carcinogenesis and Limits Clonal T Cell Responses to Chemotherapy (Blood) |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
In the K14-HPV16 transgenic mouse model of squamous carcinogenesis, activation of C5a receptor (C5aR1) in early neoplastic tissues fosters protumorigenic properties of C5aR1+ mast cells and macrophages, and in turn, suppression of CD8+ T cell cytotoxicity. Therapeutic inhibition of C5a receptor (C5aR1) with a peptide antagonist improved efficacy to paclitaxel chemotherapy associated with CXCR3-dependent CD8+ T cell activation. To investigate the effects of combination therapy on the T cell repertoire, we performed deep sequencing of the complementarity-determining region (CDR) 3 of the T cell receptor (TCR)b chain in matched tumor lysates and peripheral blood mononuclear cells (PBMCs). Intratumoral TCRβ clonotypes were hyperexpanded and increasingly detected in matched peripherally-expanded T cell populations, thereby implicating antigen-dependent peripheral priming in response to systemic C5aR1 inhibition.
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| Overall design |
Deep sequencing of the complementarity-determining region (CDR) 3 of the T cell receptor (TCR)b chain in matched tumor lysates and peripheral blood mononuclear cells (PBMCs)
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| Contributor(s) |
Medler T, Murugan D, Horton W, Kumar S, Cotechini T, Forsyth A, Leyshock P, Leitenberger J, Kulesz-Martin M, Margolin A, Werb Z, Coussens L |
| Citation(s) |
30300579 |
| |
| Submission date |
Mar 26, 2018 |
| Last update date |
Jan 30, 2020 |
| Contact name |
Lisa Coussens |
| E-mail(s) |
coussenl@ohsu.edu
|
| Organization name |
OHSU
|
| Street address |
SW Sam Jackson Park Rd
|
| City |
Portland |
| State/province |
Oregon |
| ZIP/Postal code |
97239 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (44)
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| This SubSeries is part of SuperSeries: |
| GSE112323 |
Extrinsic C5a Activation Regulates Squamous Carcinogenesis and Limits Clonal T Cell Responses to Chemotherapy |
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| Relations |
| BioProject |
PRJNA445687 |
| SRA |
SRP136451 |
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