6月22日，Cancer Research 雜志報道了通過抑制Stat3功能可強化對B細胞惡性腫瘤免疫達到治療目的,。
套細胞淋巴瘤（MCL）是侵襲性且無法治愈的B細胞非霍奇金淋巴瘤的一種亞型,。雖然病人往往最初對一線化療藥物和單克隆抗體治療反應良好,，但進一步治療的反應性卻較差，并最終導致復發(fā),。
利用免疫系統(tǒng),，誘導針對MCL的免疫特異性并為機體提供長期持久的免疫保護，也許可根除殘余的導致疾病復發(fā)的惡性細胞,。
本研究表明,，在惡性的B細胞中利用遺傳或藥物的手段抑制Stat3功能，可增強其免疫原性,，從而導致更好地活化抗原特異性CD4+ T細胞和恢復免疫耐受化T細胞的免疫反應性,。
此外，給予MCL荷瘤小鼠特定的Stat3抑制劑治療,，可導致惡性的B細胞中Stat3磷酸化和在體內(nèi)的抗淋巴瘤免疫力下降,。因此，該研究結(jié)果表明,，Stat3的抑制可作為一種治療策略,，克服腫瘤抗原的免疫耐受性和誘導機體對MCL和其他B細胞惡性腫瘤的強免疫反應。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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STAT3 INHIBITION AUGMENTS THE IMMUNOGENICITY OF B-CELL LYMPHOMA CELLS LEADING TO EFFECTIVE ANTITUMOR IMMUNITY
Fengdong Cheng1, Hongwei Wang1, Pedro Horna2, Zi Wang1, Bijal Shah1, Eva Sahakian1, Karrune Woan1, Alejandro Villagra1, Javier A Pinilla-Ibarz1, Said M. Sebti3, Mitchell R Smith4, Jianguo Tao5, and Eduardo M. Sotomayor1,*
Mantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell Non-Hodgkin's 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. The 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.
