近日,，中國(guó)科學(xué)院廣州生物醫(yī)藥與健康研究院陳小平研究組與廣州醫(yī)學(xué)院呼吸疾病研究所鐘南山院士合作開展的肺癌免疫治療實(shí)驗(yàn)研究取得了新進(jìn)展,。相關(guān)論文已于近日在線發(fā)表于美國(guó)《公共科學(xué)圖書館—綜合》（PLoS ONE）,。
研究人員發(fā)現(xiàn),，瘧原蟲感染（瘧疾）顯著抑制小鼠肺癌（Lewis肺癌）的生長(zhǎng)和轉(zhuǎn)移,，顯著延長(zhǎng)荷瘤小鼠的生存時(shí)間,；瘧原蟲感染明顯抑制腫瘤細(xì)胞的增殖,，促進(jìn)腫瘤細(xì)胞的凋亡,，抑制腫瘤血管的生成,；瘧原蟲感染激活機(jī)體天然免疫系統(tǒng)，誘導(dǎo)產(chǎn)生大量的IFN-γ和TNF-α等,，明顯增強(qiáng)NK細(xì)胞的殺傷活性,；瘧原蟲感染誘導(dǎo)機(jī)體產(chǎn)生腫瘤局部及全身系統(tǒng)性的腫瘤特異性免疫反應(yīng)，能使大約10%荷瘤小鼠的腫瘤完全消退,，并能長(zhǎng)期保存有效的腫瘤特異性免疫記憶,。研究還發(fā)現(xiàn)，瘧原蟲感染與肺癌DNA疫苗聯(lián)合應(yīng)用有明顯的協(xié)同作用,。
該項(xiàng)研究表明,，瘧原蟲感染通過激活天然免疫和特異性免疫反應(yīng)抑制腫瘤血管生成，進(jìn)而抑制腫瘤生長(zhǎng)和轉(zhuǎn)移,。該研究有著積極的應(yīng)用前景,，即瘧原蟲感染可能用于肺癌的免疫治療，也可能作為攜帶腫瘤抗原的新載體用于開發(fā)新型有效的治療性肺癌疫苗,。(生物谷Bioon.com)
doi:10.1371/journal.pone.0024407
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Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity
Lili Chen1,3, Zhengxiang He1,3, Li Qin1,3, Qinyan Li1,3, Xibao Shi1, Siting Zhao1, Ling Chen1, Nanshan Zhong2*, Xiaoping Chen1,3*
Background
Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer.
Methodology/Principal Findings
Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect.
Conclusions/Significance
Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy
