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Project

Targeting metabolism to modulate T cell effector function in metastatic melanoma

Metastatic melanoma represents a deadly disease with a 10-year
survival rate of less than 10%. Activation of the endogenous immune
system through immunotherapy has become a standard of care and
has greatly improved treatment. Drugs that induce T cell function
lead to the specific targeting and killing of tumor cells. Yet, especially
in metastatic sites, a significant subset of tumors evade the immune
system. Indeed, the tumor microenvironment (TME) represents a
hostile niche that inhibits the function of infiltrating T cells and
transforms them into an exhausted state. Recently, metabolic
reprogramming has emerged as a key hallmark of immune
responses. To support their proliferation and survival, T cells use
fuels to generate precursors required for macromolecular synthesis,
energy, and pro-survival pathways. As hyperproliferative cancer cells
possess an overactive metabolism, depletion of nutrients and
accumulation of metabolic waste products might represent a major
nutritional hurdle for infiltrating T cells. This study aims to map the
metabolic requirements of T cells within the TME, develop strategies
to potentiate T cell metabolism within this hostile niche, and thus use
metabolic therapy to reactivate exhausted T cells and drive their
cytotoxic function in immunocompromised metastasis. This project
has the potential to open a new metabolic avenue to enhance the
efficacy of immunotherapy and transform the standard of care for
metastatic melanoma.

Date:1 Jan 2022 →  Today
Keywords:Immunotherapy, Immunometabolism, Metastatic cancer, Cancer metabolism
Disciplines:Cancer biology, Regulation of metabolism, Adaptive immunology, Cancer therapy