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 language | English (US) |
|---|---|
| Pages (from-to) | 4440-4448 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 72 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 1 2012 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity
AU - Cheng, Fengdong
AU - Wang, Hongwei
AU - Horna, Pedro
AU - Wang, Zi
AU - Shah, Bijal
AU - Sahakian, Eva
AU - Woan, Karrune V.
AU - Villagra, Alejandro
AU - Pinilla-Ibarz, Javier
AU - Sebti, Said
AU - Smith, Mitchell
AU - Tao, Jianguo
AU - Sotomayor, Eduardo M.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84865779996&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-11-3619
DO - 10.1158/0008-5472.CAN-11-3619
M3 - Article
C2 - 22728650
AN - SCOPUS:84865779996
VL - 72
SP - 4440
EP - 4448
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 17
ER -