近日,，Moffitt癌癥中心研究人員證明,，在套細(xì)胞淋巴瘤（MCL）小鼠模型中抑制轉(zhuǎn)錄因子3（STAT3）信號(hào)轉(zhuǎn)導(dǎo)和激活,，有助免疫系統(tǒng)消除殘余惡性腫瘤細(xì)胞。
他們的研究結(jié)果發(fā)表在最近一期的Cancer Research雜志上,。套細(xì)胞淋巴瘤(MCL)是一種具有獨(dú)特臨床病理特征的B細(xì)胞非霍奇金淋巴瘤(NHL),約占NHL的3%～10%.主要發(fā)生在中老年人,，中位發(fā)病年齡60歲，以男性居多,，男女比例約為2∶1,。MCL過(guò)去曾有多種命名，Rappaport分類稱之為中間淋巴細(xì)胞性淋巴瘤,，Kiel分類稱之為中心細(xì)胞性淋巴瘤,，工作分類稱之為彌漫性小裂細(xì)胞淋巴瘤，在修訂的歐美分類(REAL)及WHO新分類中均稱為MCL,。目前認(rèn)為MCL是一種獨(dú)立的疾病,，具有獨(dú)特的形態(tài)學(xué)、免疫學(xué)及細(xì)胞遺傳學(xué)特征,。
在使用MCL小鼠模型的研究中,，研究人員推測(cè)，靶向抑制STAT3可能產(chǎn)生一種有效的抗淋巴瘤免疫反應(yīng),，STAT3“負(fù)調(diào)控”各種免疫細(xì)胞的炎癥反應(yīng) ,。
據(jù)Sotomayor表示，他們的工作是尋求新的免疫治療策略以此來(lái)打破腫瘤抗原的耐受性,。
在這項(xiàng)研究中,，研究人員發(fā)現(xiàn)通過(guò)基因操縱或使用藥物抑制惡性B細(xì)胞的STAT3，使這些癌細(xì)胞更易被特定的免疫細(xì)胞（T細(xì)胞）識(shí)別,。
這項(xiàng)研究得到了國(guó)家癌癥研究所資助,。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3619
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PMID:
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,et al.
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.
