Unknown,Transcriptomics,Genomics,Proteomics

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Tumor-specific CD4+ T cells eradicate established melanoma

ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus

SUBMITTER: Paul Antony

PROVIDER: E-GEOD-19904 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma.

Xie Ying Y Akpinarli Akgül A Maris Charles C Hipkiss Edward L EL Lane Malcolm M Kwon Eun-Kyung M EK Muranski Pawel P Restifo Nicholas P NP Antony Paul Andrew PA

The Journal of experimental medicine 20100215 3

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 naive tumor/self ...[more]

PMID: 20156973

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Dataset Information

Tumor-specific CD4+ T cells eradicate established melanoma

Publications

Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma.

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