Our lab investigates the interplay between T cells and tumors, with a particular focus on the molecular mechanisms that impair T cell-mediated immune responses against tumors.
The (neo) antigen-specific T cell response to tumors is a crucial component of antitumor immunity, but it is frequently compromised by various inhibitory factors within the tumor microenvironment or inherent to T cells. Among them, three interconnected events i) insufficient T cell trafficking into tumors, ii) compromised T cell activities, 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. These three areas form our research focus.
Approach
We begin by constructing physiologically or clinically relevant cell and mouse models to recapitulate the aforementioned events within the antitumor T cell response. Subsequently, we use or develop function-based genomics techniques, including genetic and chemical screening, in conjunction with molecular, biochemical, and cell biological assays, to systematically dissect these individual processes. Finally, we assess the translational potential of our findings in both in vivo and ex vivo tumor models.
Objective
We aim to 1)elaborate on the molecular and cellular basis of immune suppressive mechanisms in antitumor T cell immunity;2)Identify novel therapeutic targets and develop more effective therapeutic strategies for cancer immunotherapy.
Live cell imaging of T cell – Tumor cell interactions
Miao, B.*, Hu, Z.*, Mezzadra, R.*, Hoeijmakers, L.*, Fauster, A., Du, S., Yang, Z., Sator-Schmitt, M., Engel, H., Li, X., Broderick, C., Jin, G., Gomez-Eerland, R., Rozeman, L., Lei, X., Matsuo, H., Yang, C., Hofland, I., Peters, D., Broeks, A., Laport, E., Fitz, A., Zhao, X., Mahmoud, M. A. A., Ma, X., Sander, S., Liu, H. K., Cui, G., Gan, Y., Wu, W., Xiao, Y., Heck, A. J. R., Guan, W., Lowe, S. W., Horlings, H. M., Wang, C., Brummelkamp, T. R., Blank, C. U. #, Schumacher, T. N. M. # & Sun, C.#
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.#
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.
Jin, H., Shi, Y., Lv, Y., Yuan, S., Ramirez, C. F. A., Lieftink, C., Wang, L., Wang, S., Wang, C., Dias, M. H., Jochems, F., Yang, Y., Bosma, A., Hijmans, E. M., de Groot, M. H. P., Vegna, S., Cui, D., Zhou, Y., Ling, J., Wang, H., Guo, Y., Zheng, X., Isima, N., Wu, H., Sun, C., Beijersbergen, R. L., Akkari, L., Zhou, W., Zhai, B., Qin, W. & Bernards, R.
Huang, S., Holzel, M., Knijnenburg, T., Schlicker, A., Roepman, P., McDermott, U., Garnett, M., Grernrum, W., Sun, C., Prahallad, A., Groenendijk, F. H., Mittempergher, L., Nijkamp, W., Neefjes, J., Salazar, R., Ten Dijke, P., Uramoto, H., Tanaka, F., Beijersbergen, R. L., Wessels, L. F. & Bernards, R.
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.
