Improving immunometabolic fitness of NK cells in hypoxia to further their functional capacities in the tumor microenvironment.

Cellular cancer immunotherapy is on the rise to follow the footsteps of immune checkpoint inhibition as cancer immunotherapy breakthrough, yet only shows efficacy in haematological malignancies. Indeed, solid tumours impose various challenges on immune cells. Their tumour microenvironment (TME) is a metabolic wasteland that impairs effector immune cell functioning. Central in this TME is hypoxia, which is now recognized as barrier to immunotherapy due to effects on both tumour and immune cells. In this project, we focus on natural killer (NK) cells as effector immune cells with great potential as adoptive cell product due to inherent cytolytic capacities as well as safety and logistics profiles. Nonetheless, even when armoured with chimeric antigen receptors (CAR), NK cells fail to fully exert their function in hypoxia. Here, we will characterize and validate our lead for the development of (CAR) NK cells proficient in the hypoxic TME. This could propagate the development of next-generation of metabolically enhanced CAR NK cells against solid tumours.

Keywords:TUMOR MICROENVIRONMENT, HYPOXIA, MITOCHONDRIA, NK CELLS

Disciplines:Innate immunity, Regulation of metabolism, Cancer biology, Cancer therapy