Qiao Li, Ph.D.
My research has been in the area of developing immunotherapies for cancer using immune cells, such as T cells, B cells and dendritic cells (DCs). Recently, my research has been focused on the following two directions: B cells in cancer adoptive therapy and DC-based cancer stem cell (CSC) vaccine.
The role played by B cells in cancer immunology is complex and somewhat controversial, and has been largely neglected. We hypothesize that successful anti-cancer treatment strategy will have to appropriately stimulate both humoral as well as cellular immunity. To this end, we demonstrated that simultaneous targeting of CD3 on T cells and CD40 on B or DC cells augments the antitumor reactivity of the effector cells. We have also demonstrated that B cells can be secondarily activated to mediate antitumor responses in an adoptive transfer model either independently or in synergy with T cells. More recently, we find that adoptively transferred effector B cells can inhibit cancer spontaneous metastasis by direct killing of the tumor cells.
The CSC model represents a new paradigm for the development of cancer treatments. Conventional cytotoxic chemotherapy and immunologic approaches may kill most of the non-tumorigenic cells in a tumor, but CSCs survive due to their relative high resistance to drugs or non-responsiveness to immunotherapy. As a result, tumor relapses. We recently characterized CSC-enriched populations in two histologically distinct murine tumors (melanoma D5 and squamous cell cancer SCC7), and evaluated the antitumor immunogenicity by administering DC-based CSC vaccines in two genetically different syngeneic immunocompetent hosts. If our hypothesis can be tested in animal models, the findings may help identify innovative immunological approaches for human cancer treatment by specifically targeting cancer stem cells.
Representative Recent Publications
Iuchi, T, Teitz-Tennenbuam, S, Huang, J, Redman, B.G, Hughes, S.D., Li, M., Jiang, G., Chang, A.E., Li, Q. : IL-21 augments the efficacy of T cell therapy by eliciting concurrent cellular and humoral responses. Cancer Res. 68:4431-41, 2008.
Li, S., Yang, J., Urban, F.A., MacGregor, J.N., Hughes, D.P.M., Chang, A.E., Mcdonagh, K.T., Li, Q. : Genetically Engineered T Cells Expressing A HER2- specific Chimeric Receptor Mediate Antigen-specific Tumor Regression. Cancer Gene Therapy 15:382-392, 2008.
Yu, J., Tian, R., Chen, X., Cheng, S., Chang, A.E., Li, Q. : Antitumor Reactivity of T Cells Generated from Lymph Nodes Draining an SEA- expressing Murine B16 Melanoma and Secondarily Activated with Dendritic Cells. Int J Biol Sci. 5:135-146, 2009
Li, Q., Teitz-Tennenbaum, S., Donald, E., Li, M., Chang, A.E., In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy. J. Immunology, 183:3195-3203, 2009.
Chen J, Xia J, Liang X, Pan K Wang W, Lin L, Shao J, Wang Q, Li Y, Chen S, He J, Huang L, Ke M, Chen Y, Ma H, Zeng Z, Shou Z, Chang AE, and Li Q.: Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients. Int J Biol Sci, 7(1):53-60, 2011
Li, Q., Lao, X., Pan, Q., Ning, N., Yet, J., Xu, Y., Li, S., Chang, A.E.: Adoptive transfer of tumor reactive B cells confers host T cell immunity and tumor regression. Clinical Cancer Research, 17 (15):4987-95, 2011.
Ning, N., Pan, Q., Zheng, F., Teitz-Tennenbaum, S., Egenti, M., Yet, J., Li, M., Ginestier, C., Wicha, M.S., Moyer, J.S., Prince, M.E.P., Xu, Y., Zhang, XL., Huang, S., Chang, A.E., Li, Q.: Cancer stem cell vaccination confers significant anti-tumor immunity. Cancer Res, 72(7):1853–64, 2012
Chen, Y., Pan, K., Li, S., Xia, J., Wang, W., Chen, J., Zhao, J., Lu, L., Wang, D., Pan, Q., Li, J., Wang, Q., Li, Y., He, J., Li, Q.: Decreased expression of V-set and immunoglobulin domain containing 1 (VSIG1) is associated with poor prognosis in primary gastric cancer. J Surg Oncol. 106:286–293, 2012.
Teitz-Tennenbaum, S., Wicha, M.S., Chang, A.E., Li, Q.: Targeting cancer stem cells via dendritic cell vaccine (invited review/peer-reviewed OncoImmunology, 1(8):1401–03, 2012
Huang J, Li C, Wang Y, Lv H, Guo Y, Dai H, Wicha MS, Chang AE, Li Q: Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133(high) cancer stem cells in vitro and in vivo. Clin Immunol 149: 156-68, 2013.
Wang S, Lu L, Fan Y, Wicha MS, Cao Z, Chang AE, Xia J, Baker JR, Li Q: Characterization of a novel transgenic mouse tumor model for targeting HER2+ cancer stem cells (in press).