Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity.
Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity.
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DOI：
10.1158/0008-5472.can-11-3619
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发表时间：
2012-09-01
期刊：
影响因子：
11.2
通讯作者：
Sotomayor EM
中科院分区：
文献类型：
--
作者：
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
套细胞淋巴瘤（MCL）是一种侵袭性和不可治愈的B细胞非霍奇金淋巴瘤亚型，其特征是对化疗加单克隆抗体一线治疗的初始反应，随后复发，对进一步治疗的反应性较低。利用免疫系统引发其精致的特异性和持久的保护可能会提供持续的MCL免疫力，可能会消除导致疾病复发的残留恶性细胞。在这里，我们表明，遗传或药理学破坏Stat3在恶性B细胞增强其免疫原性，导致更好地激活抗原特异性CD4+ T细胞和耐受性T细胞的反应性恢复。额外的证据表明，用特定的Stat 3抑制剂对携带MCL的小鼠进行体内治疗会导致恶性B细胞中的Stat 3磷酸化和抗淋巴瘤免疫力降低，这表明Stat 3抑制是克服对肿瘤抗原的耐受性并引发针对MCL的强免疫力的一种诱人策略。和其他B细胞恶性肿瘤。
Mantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell Non-Hodgkin’s lymphomas characterized by an initial response to first-line treatment with chemotherapy plus monoclonal antibodies followed by relapse and less responsiveness to further lines of treatment. 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 additional demonstration that in vivo treatment of MCL-bearing mice with a specific Stat3 inhibitor resulted in decreased Stat3 phosphorylation in malignant B-cells and anti-lymphoma immunity, points to Stat3 inhibition as an enticing strategy to overcome tolerance to tumor antigens and elicit a strong immunity against MCL and other B-cell malignancies.