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Immune Regulation in Cancer

Junior Research Group Immune Regulation in Cancer

Dr. Chong Sun

Dissect antitumor T cell immunity for more effective cancer immunotherapy (click to enlarge)
© dkfz.de

Research focus
We focus on the interplay between T cells and tumors. Tumor (neo)antigen-specific T cell response constitutes a key component of antitumor immunity, but it is often compromised by various inhibitory factors in the tumor microenvironment or intrinsically residing in T cells. i) Insufficient T cell trafficking into tumors, ii) compromised T cell activation, and iii) resistance of tumor cells to cytotoxicity of T cells largely contribute to the immune evasion of cancer and render T cell-based immunotherapies futile in the majority of cancer patients.

Approach
Build physiologically or clinically relevant models to recapitulate the abovementioned three modules in antitumor T cell response. Afterward, we use function-based genomic tools (including genetic and chemical screening) in combination with biochemical and cell biological assays to systematically dissect the inhibitory events. Finally, we evaluate the translational potential of the findings in in vivo and ex vivo tumor models.

Objective

  • Elaborate on the molecular and cellular basis of immune suppressive mechanisms in antitumor T cell immunity.
  • Identify novel therapeutic targets and develop rational combinatorial strategies for cancer immunotherapies.

Contact

Dr. Chong Sun
Immune Regulation in Cancer (D250)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 3432

Selected Publications

  • Sun, C.*, Mezzadra, R.* & Schumacher, T. N.* Regulation and Function of the PD-L1 Checkpoint. Immunity 48, 434-452, doi:10.1016/j.immuni.2018.03.014 (2018).
  • Mezzadra, R.*, Sun, C.*, Jae, L. T.*, Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M. E. W., Slagter, M., Rozeman, E. A., Hofland, I., Broeks, A., Horlings, H. M., Wessels, L. F. A., Blank, C. U., Xiao, Y., Heck, A. J. R., Borst, J., Brummelkamp, T. R. & Schumacher, T. N. M. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549, 106-110, doi:10.1038/nature23669 (2017).
  • Sun, C*., Wang, L.*, Huang, S.*, Heynen, G. J., Prahallad, A., Robert, C., Haanen, J., Blank, C., Wesseling, J., Willems, S. M., Zecchin, D., Hobor, S., Bajpe, P. K., Lieftink, C., Mateus, C., Vagner, S., Grernrum, W., Hofland, I., Schlicker, A., Wessels, L. F., Beijersbergen, R. L., Bardelli, A., Di Nicolantonio, F., Eggermont, A. M. & Bernards, R. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 508, 118-122, doi:10.1038/nature13121 (2014).
  • Carette, J. E., Guimaraes, C. P., Wuethrich, I., Blomen, V. A., Varadarajan, M., Sun, C., Bell, G., Yuan, B., Muellner, M. K., Nijman, S. M., Ploegh, H. L. & Brummelkamp, T. R. Global gene disruption in human cells to assign genes to phenotypes by deep sequencing. Nat Biotechnol 29, 542-546, doi:10.1038/nbt.1857 (2011).
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