近日,Moffitt癌症中心研究人员证明,在套细胞淋巴瘤(MCL)小鼠模型中抑制转录因子3(STAT3)信号转导和激活,有助免疫系统消除残余恶性肿瘤细胞。
他们的研究结果发表在最近一期的Cancer Research杂志上。套细胞淋巴瘤(MCL)是一种具有独特临床病理特征的B细胞非霍奇金淋巴瘤(NHL),约占NHL的3%~10%.主要发生在中老年人,中位发病年龄60岁,以男性居多,男女比例约为2∶1。MCL过去曾有多种命名,Rappaport分类称之为中间淋巴细胞性淋巴瘤,Kiel分类称之为中心细胞性淋巴瘤,工作分类称之为弥漫性小裂细胞淋巴瘤,在修订的欧美分类(REAL)及WHO新分类中均称为MCL。目前认为MCL是一种独立的疾病,具有独特的形态学、免疫学及细胞遗传学特征。
在使用MCL小鼠模型的研究中,研究人员推测,靶向抑制STAT3可能产生一种有效的抗淋巴瘤免疫反应,STAT3“负调控”各种免疫细胞的炎症反应 。
据Sotomayor表示,他们的工作是寻求新的免疫治疗策略以此来打破肿瘤抗原的耐受性。
在这项研究中,研究人员发现通过基因操纵或使用药物抑制恶性B细胞的STAT3,使这些癌细胞更易被特定的免疫细胞(T细胞)识别。
这项研究得到了国家癌症研究所资助。(生物谷:Bioon.com)
doi:10.1158/0008-5472.CAN-11-3619
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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,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.