Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4440-4448
Number of pages9
JournalCancer Research
Volume72
Issue number17
DOIs
StatePublished - Sep 1 2012

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