Mechanism that mediate maintenance and differentiation of proliferation competent progenitor T cells in chronic infection (B14)

• Subject Area: Virology
• Term: from 2017 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 210592381

The so called ‘exhausted’ or hypofunctional state of T cells in tumors or chronic infections constitutes a key limitation for successful immunotherapy. With the support of this CRC, we identified the transcription factor Tox as the master regulator required for the differentiation and maintenance of exhausted T cell populations. In our project we want to separate the Tox-induced transcriptional networks that determine the phenotypic differentiation versus those controlling the maintenance and survival of the progenitor population. Moreover, ‘exhausted’ effector T cell populations are very heterogeneous. So far, the functional significance and developmental traits of these subpopulations remain unresolved. We will then resolve mechanisms that cause this diversity and unravel the specific functions that are performed by these subsets. Finally, we want to identify how checkpoint inhibiting therapies impact the different subpopulations and identify a strategy for subset specific manipulations. Altogether, we seek to advance our understanding of the transcriptional networks and molecular mechanisms that induce and maintain ‘exhausted’ T cell populations and their subsets, as well as to identify new molecular targets to improve immunotherapy.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1054: Control and Plasticity of Cell-Fate Decisions in the Immune System
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Head: Professor Dr. Dietmar Zehn