Pan Lab @ Tsinghua University
Research Topics
Our lab focuses on uncovering fundamental mechanisms and developing innovative strategies to enhance anti-tumor immunity. We investigate tumor-intrinsic pathways that regulate susceptibility to immune cell-mediated elimination, aiming to identify key drivers of immune resistance. Leveraging cutting-edge functional genomics, we engineer novel tumor–immune cell interactions to create next-generation cancer immunotherapies. In parallel, we reprogram immune cells to boost their cytotoxic activity and overcome immune suppression within the tumor microenvironment.
1. Dissecting tumor-intrinsic mechanisms governing immune cell-mediated elimination
Through cutting-edge functional genomic approaches and by establishing various in vitro and in vivo screening assays, we investigate the pathways employed by tumor cells to thwart elimination by different types of immune cells, such as CD8+ T cells, NK cells, and macrophages.By unraveling these intricate pathways, our goal is to gain a comprehensive understanding of immune evasion mechanisms, paving the way for the development of novel and effective strategies in cancer immunotherapy.
Selected publications:
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Tang K, Wu L#, Hu Y, Xue T, Jin Y, Zhou X, Luo C, Zhao Y, Tong L, Dai J, Feng D, Zeng Z# and Pan D#. Perturbation of Calreticulin potentiates CD8+ T cell-mediated anti-tumor immunity. J Exp Med, 2025 Oct 6;222(10):e20242360. doi: 10.1084/jem.20242360. Epub 2025 Aug 20. (# denotes corresponding authors)
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Luo C, Zhang R, Guo R, Wu L, Xue T, He Y, Jin Y, Zhao Y, Zhang Z, Zhang P, Ye S, Li X, Li D, Zhang W, Wang C, Lai L, Pan-Hammarström Q, Wucherpfennig KW, Gao Z#, Pan D#, Zeng Z# Integrated computational analysis identifies therapeutic targets with dual action in cancer cells and T cells. Immunity, 2025 Mar 11;58(3):745-765.e9. doi: 10.1016/j.immuni.2025.02.007. (# denotes corresponding authors)
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Wu L, Jin Y, Zhao X, Tang K, Zhao Y, Tong L, Yu X, Xiong K, Luo C, Zhu J, Wang F#, Zeng Z#, Pan D#. Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNFa. Cell Metabolism, 2023 Sep 5;35(9):1580-1596.e9. doi: 10.1016/j.cmet.2023.07.001 (# denotes corresponding authors)
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Pan D*, Kobayashi A*, Jiang P*, Andrade LF, Tay RE, Luoma A, Tsoucas D, Qiu X, Lim K, Rao P, Long HW, Yuan G, Doench J, Brown M, Liu XL, and Wucherpfennig KW. A Major Chromatin Regulator Determines Resistance of Tumor cells to T cell Mediated Killing. Science, 2018 Jan 4; pii:eaao1710 doi: 10.1126/science.aao1710. (* Denotes equal contribution)
2. Engineering novel tumor–immune cell interactions for cancer immunotherapy
The dynamic interactions between tumor cells and immune cells are fundamental in shaping anti-tumor immune responses. Dysregulation of these interactions often enables tumors to evade immune surveillance and resist immunotherapy. Our lab harnesses functional genomic approaches and antibody-based protein engineering to design innovative therapeutics that rewire tumor–immune cell communication. We develop novel protein-based drugs, including T cell engagers and bispecific antibodies, to precisely modulate immune synapses and enhance tumor cell recognition and elimination. By integrating cutting-edge screening technologies with rational drug design, we aim to pioneer next-generation cancer immunotherapies that overcome immune resistance and improve patient outcomes.​
Selected publications:
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Zhou X, Xu T, Li C, He Y, Hu Y, Gong H, Li J, Jiang H, Wen L, Fu Y, Zeng Z#, Pan D#. Potentiating anti-tumor immunity by re-engaging immune synapse molecules. Cell Reports Medicine, Feb 14:101975. doi: 10.1016/j.xcrm.2025.101975. (# denotes corresponding authors)
This paper reveal that DNA methylation-driven ICAM-1 loss confers tumorresistance to T and NK cell killing. Restoring ICAM-1/LFA-1 signaling with‘‘LFA-1 engager’’ enhances anti-tumor immunity and boosts immune checkpoint blockade, presenting a promising therapeutic strategy for ICAM-1-deficient tumors.
3. Reprogramming immune cells to enhance anti-tumor responses
The dynamic interactions between tumor cells and immune cells are fundamental in shaping anti-tumor immune responses. Dysregulation of these interactions often enables tumors to evade immune surveillance and resist immunotherapy. Our lab harnesses functional genomic approaches and antibody-based protein engineering to design innovative therapeutics that rewire tumor–immune cell communication. We develop novel protein-based drugs, including T cell engagers and bispecific antibodies, to precisely modulate immune synapses and enhance tumor cell recognition and elimination. By integrating cutting-edge screening technologies with rational drug design, we aim to pioneer next-generation cancer immunotherapies that overcome immune resistance and improve patient outcomes.​
Selected publications:
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Lu Y, Luo C, Huang L, Wu G, Zhong L, Chu J, Wang F#, Zeng Z#, and Pan D#. Functional genetic screens reveal key pathways instructing the molecular phenotypes of tumor-associated macrophages Cancer Immunology Research, 2025 https://doi.org/10.1158/2326-6066.CIR-25-0488