Stat3 Inhibition Augments the Immunogenicity of B-cell Lymphoma Cells, Leading to Effective Antitumor Immunity

Overview

Journal Cancer Res

Specialty Oncology

Date 2012 Jun 26

PMID 22728650

Citations 13

Authors

Fengdong Cheng

Hongwei Wang

Pedro Horna

Zi Wang

Bijal Shah

Eva Sahakian

Karrune V Woan

Alejandro Villagra

Javier Pinilla-Ibarz

Said Sebti

Mitchell Smith

Jianguo Tao

Eduardo M Sotomayor

Affiliations

Soon will be listed here.

Abstract

Mantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell non-Hodgkin lymphomas. Although patients often respond initially to first-line treatment with chemotherapy plus monoclonal antibodies, relapse and decreased response to further lines of treatment eventually occurs. Harnessing the immune system to elicit its exquisite specificity and long-lasting protection might provide sustained MCL immunity that could potentially eradicate residual malignant cells responsible for disease relapse. Here, we show that genetic or pharmacologic disruption of Stat3 in malignant B cells augments their immunogenicity leading to better activation of antigen-specific CD4(+) T cells and restoration of responsiveness of tolerized T cells. In addition, treatment of MCL-bearing mice with a specific Stat3 inhibitor resulted in decreased Stat3 phosphorylation in malignant B cells and anti-lymphoma immunity in vivo. Our findings therefore indicate that Stat3 inhibition may represent a therapeutic strategy to overcome tolerance to tumor antigens and elicit a strong immunity against MCL and other B-cell malignancies.

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