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

Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy Pfannenstiel and Gastman Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P171 http://www.immunotherapyofcancer.org/content/1/S1/P171 POSTER PRESENTATION Open Access Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy Lukas W Pfannenstiel , Brian R Gastman From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Published: 7 November 2013 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 doi:10.1186/2051-1426-1-S1-P171 patients, as well as years of immunotherapy development, Cite this article as: Pfannenstiel and Gastman: Tumor-induced truly effective immune-based therapies remain out of suppressive CD8+ T cells: implications for cancer immunotherapy. reach. We have previously shown that co-incubation of Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P171. 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 suppres- sive function. We further show that the tumor microenvir- onment 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 Submit your next manuscript to BioMed Central function of dysfunctional, suppressive T cells in a manner and take full advantage of: similar to previous in vitro studies. Further work will also evaluate the role of Mcl-1 expression in generation of • Convenient online submission dysfunctional CD8 T cells in vivo. • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Immunology, Cleveland Clinic, Cleveland, OH, USA © 2013 Pfannenstiel and Gastman; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

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

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Publisher
Springer Journals
Copyright
Copyright © 2013 by Pfannenstiel and Gastman; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-1-S1-P171
Publisher site
See Article on Publisher Site

Abstract

Pfannenstiel and Gastman Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P171 http://www.immunotherapyofcancer.org/content/1/S1/P171 POSTER PRESENTATION Open Access Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy Lukas W Pfannenstiel , Brian R Gastman From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Published: 7 November 2013 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 doi:10.1186/2051-1426-1-S1-P171 patients, as well as years of immunotherapy development, Cite this article as: Pfannenstiel and Gastman: Tumor-induced truly effective immune-based therapies remain out of suppressive CD8+ T cells: implications for cancer immunotherapy. reach. We have previously shown that co-incubation of Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P171. 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 suppres- sive function. We further show that the tumor microenvir- onment 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 Submit your next manuscript to BioMed Central function of dysfunctional, suppressive T cells in a manner and take full advantage of: similar to previous in vitro studies. Further work will also evaluate the role of Mcl-1 expression in generation of • Convenient online submission dysfunctional CD8 T cells in vivo. • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Immunology, Cleveland Clinic, Cleveland, OH, USA © 2013 Pfannenstiel and Gastman; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal

Journal for ImmunoTherapy of Cancer – Springer Journals

Published: Nov 7, 2013

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