alexa Lenalidomide Polarizes Th1-specific Anti-tumor Immune Response and Expands XBP1 Antigen-Specific Central Memory CD3+CD8+ T cells against Various Solid Tumors
ISSN: 2329-6917

Journal of Leukemia
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Research Article

Lenalidomide Polarizes Th1-specific Anti-tumor Immune Response and Expands XBP1 Antigen-Specific Central Memory CD3+CD8+ T cells against Various Solid Tumors

Jooeun Bae1,2*, Derin B Keskin1,2, Kristen Cowens1,2, Ann-Hwee Lee3, Glen Dranoff1,2, Nikhil C Munshi1,2,4 and Kenneth C Anderson1,2

1Dana-Farber Cancer Institute, Boston, Massachusetts, USA

2 Harvard Medical School, Boston, Massachusetts, USA

3Weill Cornell Medical College, New York, NY, USA

4VA Boston Healthcare System, Boston, Massachusetts, USA

*Corresponding Author:
Jooeun Bae
Dana-Farber Cancer Institute, Harvard Medical School
Boston, USA
Tel: 617-632-5908
Fax: +617-632-2140
E-mail: [email protected]

Received date: January 24, 2015; Accepted date: April 11, 2015; Published date: April 21, 2015

Citation: Bae J, Keskin DB, Cowens K, Lee A, Dranoff (2015) Lenalidomide Polarizes Th1-specific Anti-tumor Immune Response and Expands XBP1 Antigen- Specific Central Memory CD3+CD8+ T cells against Various Solid Tumors. J Leuk 3:178. doi: 10.4172/2329-6917.1000178

Copyright: © 2015 Bae J, et al. 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 author and source are credited.

Abstract

Introduction: Effective combination immunotherapeutic strategies may be required to enhance effector cells? anti-tumor activities and improve clinical outcomes. Methods: XBP1 antigen-specific cytotoxic T lymphocytes (XBP1-CTL) generated using immunogenic heteroclitic XBP1 US184-192 (YISPWILAV) and XBP1 SP367-375 (YLFPQLISV) peptides or various solid tumor cells overexpressing XBP1 target antigen were evaluated, either alone or in combination with lenalidomide, for phenotype and immune functional activity. Results: Lenalidomide treatment of XBP1-CTL increased the proportion of CD45RO+ memory CD3+CD8+ T cells, but not the total CD3+CD8+ T cells. Lenalidomide upregulated critical T cell activation markers and costimulatory molecules (CD28, CD38, CD40L, CD69, ICOS), especially within the central memory CTL subset of XBP1-CTL, while decreasing TCRαβ and T cell checkpoint blockade (CTLA-4, PD-1). Lenalidomide increased the anti-tumor activities of XBP1-CTL memory subsets, which were associated with expression of Th1 transcriptional regulators (T-bet, Eomes) and Akt activation, thereby resulting in enhanced IFN-γ production, granzyme B upregulation and specific CD28/CD38-positive and CTLA-4/PD-1-negative cell proliferation. Conclusions: These studies suggest the potential benefit of lenalidomide treatment to boost anti-tumor activities of XBP1-specific CTL against a variety of solid tumors and enhance response to an XBP1-directing cancer vaccine regime.

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