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 journalArticle

14 Citations (Scopus)

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
Externally publishedYes

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Mantle-Cell Lymphoma
B-Cell Lymphoma
Immunity
B-Lymphocytes
T-Lymphocytes
Recurrence
CD4 Antigens
Neoplasm Antigens
Therapeutics
Non-Hodgkin's Lymphoma
Immune System
Monoclonal Antibodies
Phosphorylation
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity. / Cheng, Fengdong; Wang, Hongwei; Horna, Pedro; Wang, Zi; Shah, Bijal; Sahakian, Eva; Woan, Karrune V.; Villagra, Alejandro; Pinilla-Ibarz, Javier; Sebti, Said; Smith, Mitchell; Tao, Jianguo; Sotomayor, Eduardo M.

In: Cancer Research, Vol. 72, No. 17, 01.09.2012, p. 4440-4448.

Research output: Contribution to journalArticle

Cheng, F, Wang, H, Horna, P, Wang, Z, Shah, B, Sahakian, E, Woan, KV, Villagra, A, Pinilla-Ibarz, J, Sebti, S, Smith, M, Tao, J & Sotomayor, EM 2012, 'Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity', Cancer Research, vol. 72, no. 17, pp. 4440-4448. https://doi.org/10.1158/0008-5472.CAN-11-3619
Cheng, Fengdong ; Wang, Hongwei ; Horna, Pedro ; Wang, Zi ; Shah, Bijal ; Sahakian, Eva ; Woan, Karrune V. ; Villagra, Alejandro ; Pinilla-Ibarz, Javier ; Sebti, Said ; Smith, Mitchell ; Tao, Jianguo ; Sotomayor, Eduardo M. / Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity. In: Cancer Research. 2012 ; Vol. 72, No. 17. pp. 4440-4448.
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