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Qi-Jing Li, PhD

Associate Professor of Immunology
Campus Mail: 303 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710
Phone: (919) 668-4070
Email: qi-jing.li@duke.edu

Recent clinical success in cancer immunotherapy, including immune checkpoint blockades and chimeric antigen receptor T cells, have settled a long-debated question in the field: whether tumors can be recognized and eliminated by our own immune system, specifically, the T lymphocyte. Meanwhile, current limitations of these advanced treatments pinpoint fundamental knowledge deficits in basic T cell biology, especially in the context of tumor-carrying patients. Aiming to develop new immunotherapies against cancers, and interconnected with clinical trials executed by clinician collaborators and immunogenomic tools developed in house, my research program rests on three pillars – the T cell, the Tumor Microenvironment, and Immunotherapy.

We regard the tumor as an acquired immunosuppressive organ. By this scientific precept, we study how tumors inhibit T cell-mediated immunity both locally and systemically. Our early TCR repertoire profiling of gastric tumors and tumor-free patient mucosa revealed the correlation between tissue resident T cell diversity and patient survival. Our recent single cell RNA sequencing study depicted complex pathways to develop T cell memory intratumorally. Currently, aided by bioinformatics and animal models, we are actively dissecting signaling pathways, transcription regulatory networks, and epigenetic programs governing T cell differentiation in the tumor microenvironment. Moving beyond the local microenvironment, our previous studies also demonstrated that tumors remotely modulate T cell antigen-priming events in the spleen. This ongoing in-depth investigation has gradually unveiled the profound impact of this “tele-education”: established tumors hijack hematopoiesis to protect themselves against T cell surveillance. The next step is to identify those evil envoys sent out by tumors carrying signals for systemic immune suppression.

The expanding boundary of T cell biology is the frontier of cancer immunotherapy. The contrast between the unprecedented success of T cell-based therapies for blood malignancies and their repeated failures against solid tumors vividly highlights our prevalent challenges: to understand how T cells can infiltrate tumors; how infiltrated T cells can resist microenvironmental suppression; and how activated T cells can form persistent memory to restrict tumor development and metastasis. During the last decade, my laboratory invested heavily in the microRNA (miRNA) field, deeming miRNAs a unique tool for T cell biology discovery. Identifying miRNA functions and targets is our path to discovering novel proteins, or novel functions of known proteins, in T cell regulation. Expression profiling and functional screening in the lab have produced many candidates to make T cells smarter and stronger. Due to their size, these miRNA candidates can be easily combined with targeting moieties to armor T cells, and we have incorporated these small weaponries, and introduced genomic manipulations on their downstream targets, into CAR-T cells for pre-clinical studies. Indeed, some of them greatly enhance CAR-T’s anti-tumor function. As a general principle, we believe that it is necessary to empower transferred CAR T or TCR-T cells with enhanced functionality against solid tumors. We also believe the T cell is a perfect platform to integrate genomic engineering for combinatory cancer therapy. Currently, we are actively involved in three such armored CAR-T or TCR-T trials for various solid tumor treatments.  

Accompanying these trials, and other immunotherapies carried out by colleagues on campus and world-wide, we design and execute comprehensive immune monitoring procedures to rationalize successes and failures. Clinical observations are smoothly deconstructed into basic but intriguing T cell questions for us to answer, and answers generated on the bench directly inform T cell designs in future trials. This is our closed circle of research and day-to-day operation.

Education and Training

  • Graduate Research, University of California - Riverside, 1997 - 2002
  • Research Assistant, Peking University (China), 1995 - 1997
  • Ph.D., University of California - Riverside, 2002
  • B.S., Peking University (China), 1996

Selected Publications

Christian, Laura S., Liuyang Wang, Bryan Lim, Dachuan Deng, Haiyang Wu, Xiao-Fan Wang, and Qi-Jing Li. “Resident memory T cells in tumor-distant tissues fortify against metastasis formation.” Cell Rep 35, no. 6 (May 11, 2021): 109118. https://doi.org/10.1016/j.celrep.2021.109118.

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Robins, Elizabeth, Ming Zheng, Qingshan Ni, Siqi Liu, Chen Liang, Baojun Zhang, Jian Guo, et al. “Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.” Cell Mol Immunol 18, no. 1 (January 2021): 150–61. https://doi.org/10.1038/s41423-019-0347-5.

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Jia, Qingzhu, Diyuan Qin, Feng He, Qichao Xie, Zhitao Ying, Yajing Zhang, Yuqin Song, et al. “Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.” Theranostics 11, no. 10 (2021): 4699–4709. https://doi.org/10.7150/thno.54546.

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Cheng, Jia-Nan, Wen Luo, Chengdu Sun, Zheng Jin, Xianghua Zeng, Peter B. Alexander, Zhihua Gong, et al. “Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy.” Sci Adv 7, no. 5 (January 2021). https://doi.org/10.1126/sciadv.abc7609.

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Wang, Qun, Yen-Yu Lin, Baojun Zhang, Jianxuan Wu, Sumedha Roy, Jeremy J. Ratiu, Yanping Xu, et al. “A mosaic analysis system with Cre or Tomato expression in the mouse.” Proc Natl Acad Sci U S A 117, no. 45 (November 10, 2020): 28212–20. https://doi.org/10.1073/pnas.2014308117.

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Qin, Diyuan, Dan Li, Benxia Zhang, Yue Chen, Xuelian Liao, Xiaoyu Li, Peter B. Alexander, Yongsheng Wang, and Qi-Jing Li. “Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.” Oncoimmunology 9, no. 1 (August 15, 2020): 1806009. https://doi.org/10.1080/2162402X.2020.1806009.

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Zheng, Ming, Xin Zhang, Yinghui Zhou, Juan Tang, Qing Han, Yang Zhang, Qingshan Ni, et al. “TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.” Ebiomedicine 47 (September 2019): 414–26. https://doi.org/10.1016/j.ebiom.2019.07.032.

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Jia, Qingzhu, Wei Wu, Yuqi Wang, Peter B. Alexander, Chengdu Sun, Zhihua Gong, Jia-Nan Cheng, et al. “Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.” Nat Commun 9, no. 1 (December 18, 2018): 5361. https://doi.org/10.1038/s41467-018-07767-w.

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Zhao, Lintao, Ran He, Haixia Long, Bo Guo, Qingzhu Jia, Diyuan Qin, Si-Qi Liu, et al. “Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells.” Nat Med 24, no. 10 (October 2018): 1536–44. https://doi.org/10.1038/s41591-018-0205-5.

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Chong, Mengyang, Tao Yin, Rui Chen, Handan Xiang, Lifeng Yuan, Yi Ding, Christopher C. Pan, et al. “CD36 initiates the secretory phenotype during the establishment of cellular senescence.” Embo Rep 19, no. 6 (June 2018). https://doi.org/10.15252/embr.201745274.

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Cheng, Zhi, Runhong Wei, Qiuling Ma, Lin Shi, Feng He, Zixiao Shi, Tao Jin, et al. “In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.” Mol Ther 26, no. 4 (April 4, 2018): 976–85. https://doi.org/10.1016/j.ymthe.2018.01.022.

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Zhang, Baojun, Qingzhu Jia, Cheryl Bock, Gang Chen, Haili Yu, Qingshan Ni, Ying Wan, Qijing Li, and Yuan Zhuang. “Glimpse of natural selection of long-lived T-cell clones in healthy life.” Proc Natl Acad Sci U S A 113, no. 35 (August 30, 2016): 9858–63. https://doi.org/10.1073/pnas.1601634113.

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Markowitz, Geoffrey J., Pengyuan Yang, Jing Fu, Gregory A. Michelotti, Rui Chen, Jianhua Sui, Bin Yang, et al. “Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.” Cancer Res 76, no. 8 (April 15, 2016): 2394–2405. https://doi.org/10.1158/0008-5472.CAN-15-1548.

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Zhang, Baojun, Si-Qi Liu, Chaoran Li, Erik Lykken, Shan Jiang, Elizabeth Wong, Zhihua Gong, et al. “MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.” Immunity 44, no. 3 (March 15, 2016): 568–81. https://doi.org/10.1016/j.immuni.2016.01.007.

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Li, Yuanyuan, Yu Wang, Liyun Zou, Xiangyu Tang, Yi Yang, Li Ma, Qingzhu Jia, et al. “Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment.” Immunity 44, no. 2 (February 16, 2016): 422–37. https://doi.org/10.1016/j.immuni.2016.01.027.

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