近日，中国科学院广州生物医药与健康研究院陈小平研究组与广州医学院呼吸疾病研究所钟南山院士合作开展的肺癌免疫治疗实验研究取得了新进展。相关论文已于近日在线发表于美国《公共科学图书馆—综合》（PLoS ONE）。
研究人员发现，疟原虫感染（疟疾）显着抑制小鼠肺癌（Lewis肺癌）的生长和转移，显着延长荷瘤小鼠的生存时间；疟原虫感染明显抑制肿瘤细胞的增殖，促进肿瘤细胞的凋亡，抑制肿瘤血管的生成；疟原虫感染激活机体天然免疫系统，诱导产生大量的IFN-γ和TNF-α等，明显增强NK细胞的杀伤活性；疟原虫感染诱导机体产生肿瘤局部及全身系统性的肿瘤特异性免疫反应，能使大约10%荷瘤小鼠的肿瘤完全消退，并能长期保存有效的肿瘤特异性免疫记忆。研究还发现，疟原虫感染与肺癌DNA疫苗联合应用有明显的协同作用。
该项研究表明，疟原虫感染通过激活天然免疫和特异性免疫反应抑制肿瘤血管生成，进而抑制肿瘤生长和转移。该研究有着积极的应用前景，即疟原虫感染可能用于肺癌的免疫治疗，也可能作为携带肿瘤抗原的新载体用于开发新型有效的治疗性肺癌疫苗。(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
