Abstract
BackgroundLung 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 FindingsAntitumor 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/SignificanceMalaria 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.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide [1]
Suppression of Lewis lung cancer (LLC) growth and metastasis development in mice by malaria parasite infection To determine the effect of malaria infection on the growth of LLC cells, we infected tumor-bearing mice seeded with a subcutaneous (s.c.) injection of LLC cells with P. yoelii 17XNL parasitized erythrocytes (LLC+Py) or with an equivalent number of uninfected erythrocytes (LLC)
We found that whereas the LLC control group exhibited a high frequency of metastasis (10 of 10 mice, 100%), metastasis in the LLC+Py group was only observed in 1 of 10 animals (P,0.0001, Fig. 1C and Fig. S2)
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide [1]. treatment methods in surgery, irradiation, and chemotherapy have been improved, prognosis remains unsatisfactory, and developing new therapeutic strategies is still an urgent demand. Immunotherapy may represent one of new therapeutic strategies for lung cancer has recently been developed [2,3,4,5]. The goal of lung cancer immunotherapy is to augment the weakened host immune response against tumors using specific and/or nonspecific immune stimulants [4,5,6]. It is clear that lung cancer often present a tolerogenic microenvironment that hampers effective antitumor immunity. New potent and efficacious immunotherapy, both augmenting antitumor immunity and counteracting tumor-mediated immunosuppression for lung cancer are needed. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
