The tumor microenvironment plays a pivotal role in cancer progression and response to treatment. Dysregulated metabolic processes within the tumor microenvironment create an immunosuppressive milieu, impairing immune cell function, promoting immune evasion, and compromising anti-tumor responses. Various factors, including intratumoral pH, oxygen levels, nutrient and lipid composition and immunomodulatory molecules, can significantly impact the efficacy of cancer immunity.
PhD project description
The aim of this project is to characterize tumor metabolites at steady state and under immunotherapy and define the impact of specific drugs that directly impact specific metabolic cues.
Required profile of candidate
Master's degree in a relevant field (e.g., cancer biology, immunology, molecular biology).
Background in tumor biology, immunology, or metabolism, with a solid understanding of cancer immunotherapy.
Experience in conducting laboratory experiments and familiarity with a range of immunological techniques.
Experience in in vivo models and allowance to work with mice (FELASA accredited course) is advantageous.
Excellent oral and written communication skills, with the ability to present complex scientific concepts clearly and concisely.
Strong organizational skills and the ability to work independently as well as collaboratively in a team environment.
Demonstrated ability to multitask, prioritize work, and meet deadlines.
Self-motivated personality that enjoys solving challenging scientific questions in a fast-paced environment.
The ideal candidate will have a tumor biology and immunology background and will be willing to conduct animal experiments in mice using innovative methods.
Publications relevant to the project
Beck, J. D. ... Vormehr, M., Kranz L. mRNA therapeutics in cancer immunotherapy. Mol. Cancer 20, 1–24 (2021). doi: 10.1186/s12943-021-01348-0
Leone RD, Powell JD. Metabolism of immune cells in cancer. Nat Rev Cancer. 2020 Sep;20(9):516-531. doi:10.1038/s41568-020-0273-y.
Öztürk S, et al. IDO1-targeted therapy does not control disease development in the Eμ-TCL1 mouse model of CLL. Cancers (2021). doi: 10.3390/cancers13081899
Sadik A, Somarribas PLF, Öztürk S*, et al. IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. Cell (2020). doi: 10.1016/j.cell.2020.07.038
Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022 Feb;21(2):141-162. doi: 10.1038/s41573-021-00339-6.
Vormehr, M. et al. A non-functional neoepitope specific CD8+ T-cell response induced by tumor derived antigen exposure in vivo. Oncoimmunology 8, 1553478 (2019). doi: 10.1080/2162402X.2018.1553478
Vormehr, M. et al. Dexamethasone premedication suppresses vaccine-induced immune responses against cancer. Oncoimmunology 9, 1758004 (2020). doi: 10.1080/2162402X.2020.1758004
Wu F, Cheng Y, Wu L, Zhang W, Zheng W, Wang Q, Cao H, Pan X, Tang W. Emerging Landscapes of Tumor Immunity and Metabolism. Front Oncol. 2020 Oct 7;10:575037. doi: 10.3389/fonc.2020.575037