Cancer Res.:抑制Stat3可强化对B细胞恶性肿瘤的免疫

6月22日，Cancer Research 杂志报道了通过抑制Stat3功能可强化对B细胞恶性肿瘤免疫达到治疗目的。

套细胞淋巴瘤（MCL）是侵袭性且无法治愈的B细胞非霍奇金淋巴瘤的一种亚型。虽然病人往往最初对一线化疗药物和单克隆抗体治疗反应良好，但进一步治疗的反应性却较差，并最终导致复发。

利用免疫系统，诱导针对MCL的免疫特异性并为机体提供长期持久的免疫保护，也许可根除残余的导致疾病复发的恶性细胞。

本研究表明，在恶性的B细胞中利用遗传或药物的手段抑制Stat3功能，可增强其免疫原性，从而导致更好地活化抗原特异性CD4+ T细胞和恢复免疫耐受化T细胞的免疫反应性。

此外，给予MCL荷瘤小鼠特定的Stat3抑制剂治疗，可导致恶性的B细胞中Stat3磷酸化和在体内的抗淋巴瘤免疫力下降。因此，该研究结果表明，Stat3的抑制可作为一种治疗策略，克服肿瘤抗原的免疫耐受性和诱导机体对MCL和其他B细胞恶性肿瘤的强免疫反应。

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.