Immunotherapy for Metastatic Cancer

My current research interest is to develop effective immunotherapy for treating metastatic cancer and to investigate the mechanisms underlying the treatment efficacy. Our focus is to combine adoptive autologous natural killer (NK) cell therapy with clinically used chemical drugs to overcome the tumor-induced immunosuppression and to trigger effective type 1 anti-tumor immune responses. For studying NK cell therapy in spontaneous metastasis, we established a method to expand NK cells with anti-tumor activities and a syngeneic orthotopic breast cancer resection and metastasis model that mimics cancer recurrence at distal site in patients after primary tumor resection. We found that the autologous NK cell therapy promotes long-term survival of tumor-resected mice with low metastatic burden and induces protective tumor-specific T cell memory. For developing treatment for high tumor burden cancer, we identified chemical drug therapies that show differential efficacy between tumor-bearing mice of different strains. Based on these findings, we aim to investigate (1) the modulation of the metastatic microenvironment by the NK cell therapy, and how it affects tumor-specific T cell response, and (2) the mechanisms underlying the drugs’ differential efficacy in different tumor models.

• Education
• Achievements & Honors
• Selected publications
• Lab members

• PDF, 1991, Dept. Mol. & Cell Biol. UC-Berkeley, USA
• PDF, 1987-1990, Ctr. Cancer Res. M.I.T., USA
• Ph.D., 1986, Dept. Biol. Sci. Illinois State Univ., USA
• BS, 1980, Dept. Nutri. & Food Sci. Fu-Jen Catholic Univ.

1. Chu, C.-L., Chen, S.-S., Wu, T.-S., Kuo, S.-C., and Liao, N.-S. (1999) Differential effects of IL-2 and IL-15 on the death and survival of activated TCRγδ+ intestinal intraepithelial lymphocytes. J. Immunol. 162:1896, 10.4049/jimmunol.162.4.1896
2. Lai, Y.-G., Gelfanova, V., Kulik, L., Chu, C.-L., Jeng, S.-W., and Liao, N.-S. (1999) IL-15 promotes survival but not effector function differentiation of CD8+ TCRαβ+ intestinal intraepithelial lymphocytes. J. Immunol. 163:5843, DOI: 10.4049/jimmunol.163.11.5843
3. Lai, Y.-G., Hou, M.-S., Hsu, Y.-W., Chang, C.-L., Liou, Y.-H., Tsai, M.-H., Lee F., and Liao, N.-S. (2008) IL-15 does not affect IEL development in the thymus but regulates homeostasis of putative precursor and mature CD8aa+ IELs in the intestine. J. Immunol. 180: 3757, DOI: 10.4049/jimmunol.180.6.3757
4. Lee, G.A., Wang, S.-W., Liou, Y.-H., Jiang, S.-T., Ko, K.-L. and Liao, N.-S.* (2011) Different NK cell developmental events require different levels of IL-15 trans-presentation. J. Immunol. 187:1212-21, DOI: 10.4049/jimmunol.1100331
5. Chang, C.-L., Lai, Y.-G., Hou, M.-S., Huang, P.-L. and Liao, N.-S.* (2011) IL-15R expressed by radiation-resistant cells is necessary and sufficient for thymic iNKT cell survival and functional maturation. J. Immunol. 187:1235-42, doi: 10.4049/jimmunol.1100270
6. Lai, Y.G., Hou, M.S., Lo, A., Huang, S.T., Huang, Y.W., Yang-Yen, H.F., Liao, N.S. (2013) IL-15 modulates the balance between Bcl-2 and Bim via Jak3/1- PI3K-Akt-ERK pathway to promote CD8αα+ intestinal intraepithelial lymphocyte survival. Eur. J. Immunol. 43: 2305, DOI: 10.1002/eji.201243026
7. Liou, Y.H., Wang, S.W., Chang, C.L., Huang, P.L., Hou, M.S., Lai, Y.G., Lee, G.A., Jiang, S.T., Tsai, C.Y., Liao, N.S. (2014) Adipocyte IL-15 regulates local and systemic NK cell development. J. Immunol. 193: 1747, DOI: 10.4049/jimmunol.1400868.
8. Hou, M.S., Huang, S.T., Tsai, M.H., Yen, C.C., Lai, Y.G., Liou, Y.H., Lin, C.K., Liao, N.S. (2015) The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nT17 cell homeostasis in the thymus. J. Autoimmunity 56: 118, doi: 10.1016/j.jaut.2014.11.003.
9. Huang, P.L., Hou, M.S., Wang, S.W., Chang, C.L., Liou, Y.H., Liao, N.S. (2015) Skeletal muscle interleukin 15 promotes CD8+ T-cell function and autoimmune myositis. Skeletal Muscle 5: 33, DOI: 10.1186/s13395-015-0058-2
10. Lee, G.A., Lai, Y.G., Chen, R.J., Liao, N.S. (2017) Interleukin 15 activates Akt to protect astrocytes from oxygen glucose deprivation-induced cell death. Cytokine 92: 68, doi: 10.1016/j.cyto.2017.01.010.
11. Lee, G.A., Lin, T.N., Chen, C.Y., Mau, S.Y., Huang, W.Z., Kao, Y.C., Ma, R.Y., Liao, N.S. (2018) Interleukin 15 blockade protects the brain from cerebral ischemiareperfusion injury. Brain Behav. Immnu. 73: 562, doi: 10.1016/j.bbi.2018.06.021.
12. Lee, G.A., Chang, C.M., Wu, Y.C., Ma, R.Y., Chen, C.Y., Hsue, Y.T., Liao, N.S.*, Chang, H.H.* (2021) Chinese herbal medicine SS-1 inhibits T cell activation and abrogates TH responses in Sjögren’s syndrome. J. Formos. Med. Assoc. 120: 651, doi: 10.1016/j.jfma.2020.07.024.
13. Huang SW, Lai YG, Liao HT, Chang CL, Ma RY, Chen YH, Liou YH, Wu ZQ, Wu YC, Liu KJ, Huang YT, Yang JL, Dai MS*, and Liao NS* (2025) Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treat low-burden metastases. eLife DOI: 10.7554/eLife.99010.3
14. Lai YG, Liao HT, Chen YH, Huang SW, Liou YH, Wu ZQ, and Liao NS (2025) cGAS and STING in host myeloid cells are essential for effective cyclophosphamide treatment of advanced breast cancer. Cancers 17:1130, DOI: 10.3390/cancers17071130