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| Status |
Public on Jan 15, 2010 |
| Title |
Tumor-specific CD4+ T cells eradicate established melanoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Adoptive transfer of CD4+ T cells (TRP-1 CD4+ T cells) specific for tyrp-1 (tyrosinase-related protein 1) eradicate established tumors (melanoma) in lymphopenic RAG-/- hosts.
In vitro differentiated CD8+ T cells have been the primary focus of immunotherapy of cancer with little focus on CD4+ T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naïve tumor/self-specific CD4+ T cells naturally differentiated into T helper type 1 (Th1) cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8+-, B-, NK and NK-T cells. Proper activation of CD4+ T cells in vivo was important for tumor clearance as naïve tumor-specific CD4+ T cells could not completely treat tumor in lymphopenic common gamma chain-deficient (gc-/-) hosts. gc signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4+ T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4+ T cells.
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| Overall design |
2 x 10^5 sorted TRP-1 CD4+ T cells were transferred i.v. into tumor-bearing RAG-/- hosts on day 7-10 after tumor challenge, and ~1 x 10^6 CD4+ T cells were isolated 1 week later by flow sorting from pooled lymph nodes (LN) or spleens. Dye-swaps were performed.
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| Contributor(s) |
Antony PA |
| Citation(s) |
20156973 |
| Submission date |
Jan 14, 2010 |
| Last update date |
May 10, 2018 |
| Contact name |
Paul Andrew Antony |
| Organization name |
University of Maryland School of Medicine
|
| Department |
Program in Molecular Microbiology and Immunology
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| Lab |
Tumor Immunology
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| Street address |
10 South Pine Street
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21201 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (4)
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| GSM497578 |
Naïve TRP-1 CD4+ T Cells Compared to TRP-1 CD4+ T Cells from Spleen of Mice Undergoing Tumor Treatment |
| GSM497579 |
Naïve TRP-1 CD4+ T Cells Compared to TRP-1 CD4+ T Cells from LN of Mice Undergoing Tumor Treatment |
| GSM497580 |
TRP-1 CD4+ T Cells from Spleen of Mice Undergoing Tumor Treatment Compared to Naïve TRP-1 CD4+ T Cells |
| GSM497581 |
TRP-1 CD4+ T Cells from LN of Mice Undergoing Tumor Treatment Compared to Naïve TRP-1 CD4+ T Cells |
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| Relations |
| BioProject |
PRJNA121935 |
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