Project number 21

Boosting the metabolic fitness of cytotoxic T-cells to fight cancer

Cancer immunotherapy has emerged as a promising antitumor strategy, based on harnessing the natural defensive barrier against tumor progression provided by a patient’s own immune system. The success of immunotherapy is, nevertheless, compromised by the innate ability of cancer cells to evade immune clearance and, eventually, overcome the immune response. A main driver of cancer immunoevasion is the metabolic outplay of immune cells by cancer cells in the tumor microenvironment, which results in the metabolic exhaustion of immune cells such as T-cells, limiting their fitness for tumor repression. Identifying and understanding the mechanisms enabling this outplay is therefore crucial for developing more effective immunotherapies for cancer. In this project we will identify the different environmental factors and the different metabolic characteristics of cancer and immune cells, and mechanistically link them to the observed outplay of immune cells. The project builds on the expertise of the Fendt lab to measure and computationally model metabolism and on the expertise of the Van Ginderachter lab to dissect immune cell and specifically T-cell function. The understanding from this project will enable the design of therapeutic strategies to enhance the metabolic fitness of immune cells in the restrictive tumor microenvironment. In synergy with current immunotherapies, such strategies will result in highly effective anti-tumor treatments, improving the survival of cancer patients by boosting the fitness and function of their own immune system.

Keywords
immunotherapy, metabolism, T-cells, tumor microenvironment, cancermmunotherapy, metabolism, T-cells, tumor microenvironment, cancer

Supervisors
Sarah-Maria Fendt, VIB Vesalius Research Center, KU Leuven, Leuven
Jo Van Ginderachter, VIB Lab of Myeloid Cell Immunology, ​VUB, Brussel