The major goal of my research program is to elucidate the role of a common cytokine receptor ϒ chain family member IL-9 in the regulation of tumor immunity. Collectively, we revealed an IL-9-dependent antitumor response of IL-9-producing T cells, which was qualitatively and quantitatively superior to the immune response induced by Type I cytotoxic T cells, indicating that these subsets of T cells may be used to treat human cancers with greatly enhanced efficacy compared to the cells currently used in the clinic. A commentary written by Dr. Edgar Schmitt and Dr. Tobias Bopp in J Clin Invest 2013 comments that my work revealed an amazing new function of the “old” cytokine IL-9. Our current efforts are focused on the potential and the cellular mechanism of Th9 cells as a new paradigm of CD4+ T cells to eradicate advanced tumors.
Adoptive T cell therapy, Car T cells, Th9 cells, Tumor microenvironment, Immuno-checkpoint blockade, Pancreatic and Breast cancer
Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma.. Wang Q, Yong Lu, Li R, Jiang Y, Zheng Y, Qian J, Bi E, Zheng C, Hou J, Wang S, Yi Q.. Leukemia. 2017 Jun 19.
p38 MAPK-inhibited dendritic cells induce superior antitumour immune responses and overcome regulatory T-cell-mediated immunosuppression.. Yong Lu, Mingjun Zhang, Siqing Wang, Bangxing Hong, Zhiqiang Wang, Haiyan Li et al. Nature communications 2014 Jun 24;5:4229
Tumor-specific CD8+ Tc9 cells are superior effector than Tc1 cells for adoptive immunotherapy of cancers.. Yong Lu, Hong Bangxing, Li Haiyan, Zheng Yuhuan, Zhang Mingjun, Wang Siqing, Qian Jianfei, Yi Qing. Proc. Natl. Acad. Sci. U.S.A 2014 Feb 11;111(6):2265-70
Th9 cells promote antitumor immune responses in vivo Yong Lu, Sungyoul Hong, Haiyan Li, Park Junsung, Hong Bangxing, Wang Lijuan, Zheng Yuhuan et al. "." The Journal of Clinical Investigation 2012, 122(11): 4160-4171.
Yong Lu*, Wang Q, Xue Gang, Bi E, Ma X, Wang A, Qian J, Dong C and Yi Q*. Th9 cells represent a new paradigm of CD4+ T cells endowed with the ability to eradicate advanced tumors. Cancer Cell, 2018, May; In Press. (*, Corresponding authors)
Bi E*, Ma X*, Lu Y*, Yang M., Wang Q, Xue G and Yi Q. (2017). Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7. Science Signaling, Oct 2017; 9741. (*, Co-first authors)
Wang Qiang*, Yong Lu*, Li R, Jiang Y, Zheng Y, Qian J, Bi E, Zheng C, Hou J, Wang S, Yi Q. Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia. 2017 Jun 19. (*, Co-first author)
Yinghua Zhao, Xiao Chu, Jintong Chen, Ying Wang, Sujun Gao, Yuxue Jiang, Xiaoqing Zhu, Guangyun Tan, Wenjie Zhao, Huanfa Yi, Honglin Xu, Xingzhe Ma, Yong Lu*, Qing Yi*, Siqing Wang*. "Dectin-1-activated dendritic cells trigger potent antitumor immunity through the induction of Th9 cells." Nature communications 2016 (*, Corresponding authors).
Yong Lu, Mingjun Zhang, Siqing Wang, Bangxing Hong, Zhiqiang Wang, Haiyan Li et al. "p38 MAPK-inhibited dendritic cells induce superior antitumour immune responses and overcome regulatory T-cell-mediated immunosuppression." Nature communications 2014 Jun 24;5:4229
Yong Lu, Hong Bangxing, Li Haiyan, Zheng Yuhuan, Zhang Mingjun, Wang Siqing, Qian Jianfei, Yi Qing. "Tumor-specific CD8+ Tc9 cells are superior effector than Tc1 cells for adoptiveimmunotherapy of cancers." Proc. Natl. Acad. Sci. U.S.A 2014 Feb 11;111(6):2265-70
Yong Lu, Sungyoul Hong, Haiyan Li, Park Junsung, Hong Bangxing, Wang Lijuan, Zheng Yuhuan et al. "Th9 cells promote antitumor immune responses in vivo." The Journal of Clinical Investigation 2012, 122(11): 4160-4171.
Yong Lu, Wang Qiang, Yi Qing. Anticancer Tc9 cells: Long-lived tumor-killing T cells for adoptive therapy. Oncoimmunology. 2014 May 1;3(5):e28542.
Yong Lu, and Qing Yi. "Utilizing TH9 cells as a novel therapeutic strategy for malignancies." OncoImmunology 2013, 2(3): e23084 1-3.
Yong Lu, Huiyong Zhang, Jing Hou et al. "Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo." Gene Therapy 2010, 17(4): 459-468.
Yong Lu, Yunxiao Sun, Qiyan Xiong, Yu Zhang, Jing Hou, Mekoo JL Didier, Fan Zhang et al. "Immunization with P277 induces vascular leak syndrome in C57BL/6 mice via endothelial damage." Autoimmunity 2010, 43(8): 654-663.
Yong Lu, Kedong Ouyang, Jing Fang, Huiyong Zhang, Guojun Wu, Yanjun Ma, Yu Zhang et al. "Improved efficacy of DNA vaccination against prostate carcinoma by boosting with recombinant protein vaccine and by introduction of a novel adjuvant epitope." Vaccine 2009, 27(39): 5411-5418.
Yong Lu, Huiyong Zhang, Jing Fang, Huaqian Wang, Kejun You, Yanan Yang, Suli Liu et al. "Study on preparation and unique properties of a novel insulin analogue with N-terminal Arg-4, Pro-3, Lys-2, Pro-1extension at insulin B-chain." Regulatory Peptides 2009, 157(1): 92-98.
Yong Lu, Mekoo JL Didier, Kedong Ouyang, Xiangbing Hu, Yanhua Liu, Ming Lin, Liang Jin et al. "Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo." Endocrine-Related Cancer 2009, 16(4): 1171-1184.
Yong Lu, Huaqian Wang, Kedong Ouyang, Huiyong Zhang, Xiangbing Hu, Taiming Li, Rongyue Cao, and Jingjing Liu. "A DNA vaccine targeting gastrin-releasing peptide with high immunogenicity and its inhibitory action on the growth of prostate carcinoma in vivo." Pharmaceutical Biotechnology 2009, (5): 393-398.
Yong Lu, Jing Yang, and Qing Yi. "Signaling of tumor-induced immunosuppression of dendritic cells." The Tumor Immunoenvironment, pp. 339-360. Springer Netherlands, 2013. (Book Chapter)
Li Haiyan*, Yong Lu*, Qian Jianfei, et al. Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell-Derived IFN- and CD40 Ligand In Vitro. Journal of Bone and MineralResearch. 2014 Dec 1;29 (12):2666-75. (*, Co-first author)
Huiyong Zhang*, Yong Lu*, Mekoo JL Didier, Yu Zhang, Jing Fang, Rongyue Cao, and Jingjing Liu. "Enhanced inhibition of murine prostatic carcinoma growth by immunization with or administration of viable human umbilical vein endothelial cells and CRM197." Brazilian Journal of Medical and Biological Research 2011, 44(2): 140-148. (*, Co-first author)
Jing Fang*, Yong Lu*, Kedong Ouyang, Guojun Wu, Huiyong Zhang, Yanhua Liu, Yingying Chen et al. "Specific antibodies elicited by a novel DNA vaccine targeting gastrin-releasing peptide inhibit murine melanoma growth in vivo." Clinical and Vaccine Immunology 2009, 16(7): 1033-1039. (*, Co-first author)
Huiyong Zhang, Yong Lu, Yunxiao Sun, Wuling Zhu, Jingjing Liu, and Taiming Li. "Generation of a chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein and its comparative activity." Protein and Peptide Letters 2013, 20(8): 947-954.
Jing Hou, Yong Lu, Haiyan Liu, Yanjun Ma, Yun Xing, Yu Zhang, Taiming Li et al. "Oral administration of lactococcus lactis delivered heat shock protein 65 attenuates atherosclerosis in low-density lipoprotein receptor-deficient mice." Vaccine 2011, 29(24): 4102-4109.
Yanjun Ma, Yong Lu, Jing Hou, Yuankai Dong, Mingzhu Du, Yun Xing, Chiyu Ge et al. "Vaccination of non-obese diabetic mice with a fragment of peptide P277 attenuates insulin-dependent diabetes mellitus." International Immunopharmacology 2011, 11(9): 1298-1302.
Yunxiao Sun, Yong Lu, Zhufang Li and Qiang Xu et al, "Immunology effects of anti-atherosclerosis protein vaccines based on heat shock protein 65." Chinese Journal of Biotechnology 2011, 31(1): 12-18.
Huiyong Zhang, Yong Lu, Yuhan Meng, Rongyue Cao, Jingjing Liu, and Taiming Li. "The preliminary study on VEGF 183 (132-158) as one kind of protein drug carrier binding with the extracellular matrix." Pharmaceutical Biotechnology 2010, 17(3): 198-202.
Ming Lin, Yong Lu, Yu Zhang, Yanfei Xie, Xiangbing Hu, Huaqian Wang, Taiming Li, Jie Wu, Jingjing Liu, and Rongyue Cao. "Study on HSP65 DNA vaccine in the hamatogenous metastasis of B16/F10 melanoma." Pharmaceutical Biotechnology 2009, 16(2): 118-122.
Kejun You, Yong Lu, Ming Lin, Jing Kong, Rongyue Cao, Jingjing Liu, Hao Fan, and Li Zong. "Preparation and pharmacodynamics study of a novel rapid-acting analog of human insulin." Pharmaceutical Biotechnology 2009, 16(4): 334-337.
Suli Liu, Yong Lu, Xuejun Wang, Rongyue Cao, Jingjing Liu, Hao Fan, and Taiming Li. "Construction, preparation and properties of a novel short-acting human insulin analog." Journal of Southeast University (Medical Science Edition) 2009, 28(5): 371-375.
Aihua Zhu, Yong Lu, Liang Jin, Jie Wu, Taiming Li and Jingjing Liu. "Improved efficacy of P277 fused to heat shock protein 65 of mycobacterium tuberculosis against diabetes in nonobesediabetic mice." Chinese Journal of Biotechnology 2008, 24(4): 640-645.
Juefen Gu, Yong Lu. "Progresses in development of tumor target therapy with immunoconjugates constructed by monoclonal antibody and antitumor antibiotics." Chinese Journal of Medical Biotechnology 2006, 12(4):1-5
Zheng Y, Wang Q, Li T, Qian J, Lu Yong, Li Y, Bi E, Reu F, Qin Y, Drazba J, Hsi E. Role of myeloma-derived MIF in myeloma cell adhesion to bone marrow and chemotherapy response. JNCI: Journal of the National Cancer Institute. 2016 Nov 1;108(11).
Xiong Qiyan, Feng Jiao, Zhang Yu, Sun Yunxiao, Yong Lu, Li Taiminig, et al. Promotion of atherosclerosis in high cholesterol diet-fed rabbits by immunization with the P277 peptide. Immunology letters. 2016 Feb 29;170:80-7.
Hong Bangxing, Li Haiyan, Zhang Mingjun, Xu Jinda, Yong Lu, Zheng Yuhuan, Qian Jjianfei et al. p38 MAPK inhibits breast cancer metastasis through regulation of stromal expansion. International Journal of Cancer. 2015 Jan 1;136(1):34-43.
Zhang Mingjun, He Jin, Liu Zhiqiang, Yong Lu, Zheng Yuhan, Li Haiyan et al. Anti-β2-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy. Oncotarget. 2015 Apr 20;6(11):8567.
Liu Zhiqiang, Xu Jinda, He Jin, Zheng Yuhuan, Li Hanyan, Yong Lu, Qian Jianfei, Lin Pei et al. A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance. Blood. 2014 Sep 25;124(13):2061-71.
Hong Bangxing, Li Haiyan, Yong Lu, Zhang Mingjun, Zheng Yuhan, Qian Jianfei, Yi Qing. USP18 is crucial for IFN-γ-mediated inhibition of B16 melanoma tumorigenesis and antitumor immunity. Molecular cancer. 2014 May 31;13(1):1.
Zhang Mingjun, Qian Jianfei, Lan Yongsheng, Yong Lu, Li Haiyan, Hong Bangxing et al. Anti‐β2M monoclonal antibodies kill myeloma cells via cell‐and complement‐mediated cytotoxicity. International Journal of Cancer. 2014 Sep 1;135(5):1132-41.
Park Junsung, Li Haiyan, Zhang Mingjun, Yong Lu, Hong Bangxing, Zheng Yuhuan et al. Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy. Cancer Immunology, Immunotherapy. 2014 Aug 1;63(8):835-45.
Yanjun Ma, Jingjing Liu, Jing Hou, Yuankai Dong, Yong Lu, Liang Jin, Rongyue Cao et al. Oral administration of recombinant Lactococcus lactis expressing HSP65 and tandemly repeated P277 reduces the incidence of type I diabetes in non-obese diabetic mice. PloS one. 2014 Aug 26;9(8):e105701.
Lijuan Wang, Jianfei Qian, Yong Lu, Haiyan Li, Hanying Bao, Donghua He, Zhiqiang Liu et al. "Immune evasion of mantle cell lymphoma: expression of B7-H1 leads to inhibited T-cell response to and killing of tumor cells." Haematologica 2013, 98(9):1458-1466.
Liu Zhiqiang, Xu Jinda, Li Haiyan, Zheng Yuhuan, He Jin, Liu Huan, Yong Lu, Hong Bangxing et al. Bone marrow stromal cells derived MCP-1 reverses the inhibitory effects of multiple myeloma cells on osteoclastogenesis by upregulating the RANK expression. PloS one. 2013 Dec 10;8(12):e82453.
Maolei Xu, Ling Zhou, Peng Zhang, Yong Lu, Chiyu Ge, Wenjun Yao, Yun Xing et al. "Enhanced antitumor efficacy by combination treatment with a human umbilical vein endothelial cell vaccine and a tumor cell lysate-based vaccine." Tumor Biology 2013, 34(5): 3173-3182.
Jin He, Zhiqiang Liu, Yuhuan Zheng, Jianfei Qian, Haiyan Li, Yong Lu, Jingda Xu et al. "p38 MAPK in myeloma cells regulates osteoclast and osteoblast activity and induces bone destruction." Cancer Research 2012, 72(24): 6393-6402.
Lijuan Wang, Yi Zhao, Jianfei Qian, Luhong Sun, Yong Lu, Haiyan Li, Yi Li, Jing Yang, Zhen Cai, and Qing Yi. "Toll‐like receptor‐4 signaling in mantle cell lymphoma." Cancer 2012, 119(4): 782-91.
Jing Yang, Jin He, Ji Wang, Yabing Cao, Jianhua Ling, Jianfei Qian, Yong Lu et al. "Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma." Leukemia 2012, 26(9): 2114-2123.
Yuhuan Zheng, Jing Yang, Jianfei Qian, P. Qiu, Shino Hanabuchi, Yong Lu, Z. Wang et al. "PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma." Leukemia 2012, 27(3): 702-710.
Sungyoul Hong, Jianfei Qian, Haiyan Li, Jing Yang, Yong Lu, Yuhuan Zheng, and Qing Yi. "CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma." Cancer Immunology, Immunotherapy 2012, 61(4): 561-571.
Jianfei Qian, Yuhuan Zheng, Chengyun Zheng, Lijuan Wang, Hong Qin, Sungyoul Hong, Haiyan Li, Yong Lu et al. "Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma." Blood 2012, 119(1): 161-169.
Yuhuan Zheng, Jing Yang, Jianfei Qian, Liang Zhang, Yong Lu, Haiyan Li, Heather Lin et al. "Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone." Journal of Molecular Medicine 2012, 90(6): 695-706.
Sungyoul Hong, Haiyan Li, Jianfei Qian, Jing Yang, Yong Lu, and Qing Yi. "Optimizing dendritic cell vaccine for immunotherapy in multiple myeloma: tumour lysates are more potent tumour antigens than idiotype protein to promote anti‐tumour immunity." Clinical & Experimental Immunology 2012, 170(2): 167-177.
Runting Yin, Rubing Wang, Guo Le, Wei Zhang, and Yong Lu. "MiR-17-3p inhibits angiogenesis by downregulating Flk-1 in the cell growth signal pathway." Journal of Vascular Research 2012, 50(2): 157-166.
Zhang Yu, Qiyan Xiong, Xiangbing Hu, Yunxiao Sun, Xiying Tan, Huiyong Zhang, Yong Lu, and Jingjing Liu. "A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice." Heart and Vessels 2012, 27(4): 411-418.
Chiyu Ge, Yun Xing, Qi Wang, Wen Xiao, Yong Lu, Xiangbing Hu, Zhenqiu Gao et al. "Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432." International Immunopharmacology 2011, 11(12): 2200-2207.
Xiangbing Hu, Yankai Zhang, Ming Lin, Yong Lu, Yu Zhang, Huiyong Zhang, Yingying Chen et al. "The fusion protein of HSP65 with tandem repeats of β-hCG acting as a potent tumor vaccine in suppressing hepatocarcinoma." International Immunopharmacology 2010, 10(2): 230-238.
Liang Jin, Aihua Zhu, Yu Wang, Yong Lu, and Jingjing Liu. "HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration." Vaccine 2010, 28(19): 3312-3317.
Huaqian Wang, Huiyong Zhang, Jie Yang, Yong Lu, Taiming Li, Liang Jin, Rongyue Cao, and Jingjing Liu. "Genetic fusion of glutamic acid decarboxylase 65 derived peptides to the B-subunit of cholera toxin and its retardation effect of diabetes in NOD mice." Pharmaceutical Biotechnology 2009, 16(4):296-301.
Huaqian Wang, Jie Yang, Liang Jin, Jiao Feng, Yong Lu, Yunxiao Sun, Taiming Li et al. "Immunotherapy of autoimmune diabetes by nasal administration of tandem glutamic acid decarboxylase 65 peptides." Immunological Investigations 2009, 38(8): 690-703.
Aihua Zhu, Wentao Liu, Yong Lu, Liang Jin, Yu Wang, and Jingjing Liu. "Expression and purification of peptide P277 and its primary pharmacology." Journal-Yangzhou University Agricultural and Life Sciences Edtion 2007, 28(4): 13-17.
Aihua Zhu, Jingjing Liu, Wentao Liu, Yong Lu et al. "Effect of heat shock protein 65 of mycobacterium tuberculosis on prevention of diabetes in nonobese diabetic mice. " China Practical Medicine, 2007, 2(36):1-4.