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Immune Regulation in Cancer

Junior Research Group Immune Regulation in Cancer

Dr. Chong Sun

Live cell imaging of T cell – Tumor cell interaction. Red: PD-1(on T cells); Yellow: PD-L1(on tumour cells); Cyan: CMTM6(on tumour cells)

Cancer initiation and progression rely on an intricate signaling network that not only intracellularly fuels the proliferation and survival of cancer cells, but in the meantime, suppresses the immune system through intercellular interactions in the tumor microenvironment. Cancer immunotherapies that aim to abate the immune suppressive mechanisms such as immune checkpoint blockade therapies have achieved remarkable clinical success, which is highlighted by many cases of long-lasting remissions in patients with advanced cancer. However, the majority of cancer patients do not benefit from the current immunotherapies while unfortunately, the mechanisms of therapeutic resistance are largely unclear and alternative effective treatment options have yet to be established. These critical unmet needs in the clinic necessitate detailed and function-based investigations of the regulatory mechanisms in the process of anti-tumor immune responses.

Genome-wide functional genetic screening provides a powerful tool to assign genes to phenotypes in an unbiased and systematic manner. We have been using and developing this technology in combination with techniques in cell biology and biochemistry to study i) treatment-induced intracellular signaling rewiring2,3 and ii) intercellular signaling that modulates cell-cell interactions1. The mechanistic insights from our previous studies have given rise to multiple clinical trials (one of them has yielded positive outcomes in phase 3) and led to the identification of novel regulators and interacting partners of the PD-L1 checkpoint1. In addition to the function-based screening technologies, our expertise extends to T cell-centered molecular cell biology.

Tumor (neo) antigen-specific T cell responses constitute a key component of antitumor immunity but harbor high-dimensional complexity. T cell immunity can become compromised at every stage in the cancer immunity cycle, including inadequate T cell priming, inefficient trafficking of T cells into tumors, resistance of tumors to the cytotoxicity of T cells, and suppressive signaling delivered by other cells in the tumor microenvironment. In the coming years, we will apply our expertise in functional genetics and T cell biology in the respective cell and mouse models to study the interactions between T cells and tumor cells, and also T cells and other immune cells. We aim to identify and characterize the molecular determinants in the complex process of antitumor T cell responses, and eventually evaluate their therapeutic potentials in the forms of monotherapies or rationally designed combinatorial treatment strategies.


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

Selected Publications

  • R. Mezzadra*, C. Sun*, L. T. Jae*, R. Gomez-Eerland, E. de Vries, W. Wu, M. E. W. Logtenberg, M. Slagter, E. A. Rozeman, I. Hofland, A. Broeks, H. M. Horlings, L. F. A. Wessels, C. U. Blank, Y. Xiao, A. J. R. Heck, J. Borst, T. R. Brummelkamp, T. N. (2017). Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature
  • C. Sun*, L. Wang*, S. Huang*, G. J. Heynen, A. Prahallad, C. Robert, J. Haanen, C. Blank, J. Wesseling, S. M. Willems, D. Zecchin, S. Hobor, P. K. Bajpe, C. Lieftink, C. Mateus, S. Vagner, W. Grernrum, I. Hofland, A. Schlicker, L. F. Wessels, R. L. B (2014). Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature
  • A. Prahallad*, C. Sun*, S. Huang*, F. Di Nicolantonio*, R. Salazar, D. Zecchin, R. L. Beijersbergen, A. Bardelli, R. Bernards (2012). Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature
  • C. Sun*, R. Mezzadra*, T. N. Schumacher* (2018). Regulation and Function of the PD-L1 Checkpoint. Immunity (* equal contribution)
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