1. Targeting Immune Evasion Mechanisms in Cancer
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:
-
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, In Press. (# denotes corresponding authors)
-
Ito Y*, Pan D*, Zhang W, Zhang X, Juan TY, Pyrdol JW, Kyrysyuk O, Doench JG, Liu XS, Wucherpfennig KW. Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-Secreted Cytokines. Cancer Discov. 2023 May 4;13(5):1186-1209. doi: 10.1158/2159-8290.CD-22-1125. (* Denotes equal contribution)
-
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. Identification of key functional interactions in the tumor microenvironment
Tumor microenvironment (TME) is highly immune suppressive. Targeting the interactions of key negative regulators of anti-tumor immunity (e.g., PD-1/PD-L1) could effectively boost the anti-tumor immune response. Through the integration of functional genetic perturbation and single-cell technologies, we aim to map the key immune regulatory and druggable interactions in the tumor microenvironment. By deciphering these crucial interactions, the ultimate goal is the development of targeted therapies that can effectively potentiate anti-tumor immunity.