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Volume 1 Supplement 1

Abstracts of the 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

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Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy

The immune system has the potential to be a powerful tool to destroy tumors; however despite ample evidence of endogenous anti-tumor immune responses in many patients, as well as years of immunotherapy development, truly effective immune-based therapies remain out of reach. We have previously shown that co-incubation of normal human T cells with various tumor lines can induce dysfunctional changes in the T cells characterized by the loss of CD27/CD28 expression, hypo-proliferation upon activation, and the gain of suppressive function in vitro. We also found that this process could be inhibited by IL-7 signaling, primarily through PI3k/AKT signaling, and enhancing the expression of the pro-survival molecule Mcl-1. In the current study, we use a mouse model of HPV+ head and neck cancer to show that the process of tumor-induced dysfunction also induces the expression of PD-1 in both human and mouse T cells, and that tumor-exposed mouse T cells are also capable of suppressive function. We further show that the tumor microenvironment induces large numbers of PD-1+ CD8+ T cells that are also positive for other negative regulators of T cell function including Tim-3, and that these cells are also suppressive ex vivo. Ongoing work will establish whether blockade of PD-1 and Tim-3, as well as in vivo systemic treatment with IL-7 concurrent with adoptive transfer of tumor-specific T cells is able to resist the induction and function of dysfunctional, suppressive T cells in a manner similar to previous in vitro studies. Further work will also evaluate the role of Mcl-1 expression in generation of dysfunctional CD8 T cells in vivo.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Pfannenstiel, L.W., Gastman, B.R. Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy. j. immunotherapy cancer 1 (Suppl 1), P171 (2013).

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