Adaptive Resistance

Objectives and Challenges

The team led by Caroline Robert is conducting research organized around three objectives: the implementation of a database currently comprising more than 2,000 patients with melanoma; the continuation of the Melavatar program within the tumor bank associated with this database; and thethe identification of early markers of treatment efficacy and/or toxicity in order to develop an algorithm applicable in clinical practice; and the preclinical development of new therapies to combat treatment resistance by targeting the adaptability of cancer cells and cells in the tumor microenvironment.

Research Areas/Major Projects

The main research projects focus on the links between the RNA translation process and lymphocyte maturation/exhaustion, the characterization of the relationship between persistent cells and the immune system, the identification of biomarkers before and early during treatment to predict therapeutic efficacy, and the investigation of tumor persistence in the central nervous system. 

Within the team, the group led by Anne Chauchereau studies the mechanisms regulating translation as an adaptive mechanism of resistance to prostate cancer treatments and focuses on the functions of endoplasmic reticulum proteins (FKBP7) and translational regulators (ABCFs). The PDX models and organoids established in the unit are used to determine the therapeutic relevance of the identified targets.

Major Findings and Scientific, Clinical, and Societal Impacts

The team’s work has led to the discovery of an immune evasion mechanism in persistent cells via the secretion of the MIF factor, which can be targeted therapeutically, the demonstration of the major role of translation regulation via the eIF4F factor in lymphocyte maturation and exhaustion, the demonstration of a synergistic effect between PD-1 blockade and eIF4A inhibitors in human and murine preclinical models; and the identification of an algorithm to predict the efficacy of immunotherapies for patients with metastatic melanoma.