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Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM

Cellular & Molecular Immunology volume 8, pages 359–367 (2011)Cite this article

Abstract

Trichosanthin (TCS), extracted from the Chinese medicinal herb Trichosanthes kirilowi, has shown promise for the inhibition of tumor growth. However, its immunomodulatory effect on tumor–host interaction remains unknown. In this study, we focused on the effect of TCS on murine anti-tumor immune response in the 3LL Lewis lung carcinoma tumor model and explored the possible molecular pathways involved. In addition to inhibiting cell proliferation and inducing apoptosis in the 3LL tumor, TCS retarded tumor growth and prolonged mouse survival more significantly in C57BL/6 immunocompetent mice than in nude mice. This reflected the fact that the host immune system was involved in tumor eradication. Using FACS analysis, we found that TCS increased the percentage of effector T cells, particularly Interferon-gamma (IFN-γ) producing CD4+ and CD8+ T cells from tumor-bearing mice. TCS also promoted the vigorous proliferation of antigen-specific effector T cells, markedly increased Th1 cytokine secretion and elicited more memory T cells in tumor-bearing mice, consequently enhancing the anti-tumor response and inducing immune protection. Furthermore, we found that TCS upregulated the expression of tumor suppressor in lung cancer 1 (TSLC1) in 3LL tumor cells and the expression of its ligand, class I-restricted T cell-associated molecule (CRTAM), in effector T cells. Blocking TSLC1 expression with small interfering RNA (siRNA) significantly eliminated the effects of TCS on the proliferation and cytokine secretion of effector T cells, suggesting that TCS enhances anti-tumor immune response at least partially by boosting the interaction between TSLC1 and CRTAM. Collectively, our data demonstrate that TCS not only affects tumor cells directly, but also enhances anti-tumor immunity via the interaction between TSLC1 and CRTAM. These findings may lead to the development of a novel approach for tumor regression.

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Acknowledgements

This work was supported by the National Key Technologies R&D Program of China during the Eleventh Five-Year Plan Period (2009ZX10004-104 and 2009ZX09301-011), National Science Foundation of China (30872378 and 81072408), the Science and Technology Commission of Shanghai Municipality (10JC1401100) in China and National 973 Project (2010CB912603 and 2011CB910400) in China. We thank the editors of Editage Company for professional editing of the article.

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  1. Yuchan Cai and Shudao Xiong: These authors contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Immunology, Shanghai Medical College, Key Laboratory of Molecular Medicine of Ministry of Education, Fudan University, Shanghai, China

    Yuchan Cai, Shudao Xiong, Yijie Zheng, Feifei Luo, Pei Jiang & Yiwei Chu

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  1. Yuchan Cai
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Correspondence to Yiwei Chu.

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Cai, Y., Xiong, S., Zheng, Y. et al. Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM. Cell Mol Immunol 8, 359–367 (2011). https://doi.org/10.1038/cmi.2011.12

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