Anais Elewaut wird in Anerkennung ihrer Veröffentlichung Cancer cells impair monocyte-mediated T cell stimulation to evade immunity ausgezeichnet.
The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses. Within the tumour microenvironment, CD8+ T cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches. Although interactions with type 1 conventional dendritic cells (cDC1s) have been implicated in this process, the underlying cellular players and molecular mechanisms remain incompletely understood. Here we show that inflammatory monocytes can adopt a pivotal role in intratumoral T cell stimulation. These cells express Cxcl9, Cxcl10and Il15, but in contrast to type 1 conventional dendritic cells, which cross-present antigens, inflammatory monocytes obtain and present peptide–major histocompatibility complex class I complexes from tumour cells through ‘cross-dressing’. Hyperactivation of MAPK signalling in cancer cells hampers this process by coordinately blunting the production of type I interferon (IFN-I) cytokines and inducing the secretion of the bioactive lipid, prostaglandin E2 (PGE2), which impairs the inflammatory monocyte state and intratumoral T cell stimulation. Enhancing IFN-I cytokine production and blocking PGE2 secretion, either genetically or pharmacologically, restores this process and re-sensitizes tumours to T cell-mediated immunity. Together, our work uncovers a central role of inflammat-ory monocytes in intratumoral T cell stimulation, elucidates how oncogenic signal-ling disrupts T cell responses through counter-regulation of PGE2 and IFN-I, and proposes rational combination therapies to enhance immunotherapies.
Anais performed her Master's degree in Biochemistry and Biotechnology with a major focusing on biomedical biotechnology at the University of Ghent in Belgium. She then pursued a PhD in the lab of Dr. Anna C. Obenauf at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria investigating how oncogenic signalling and tumour-derived factors remodel the tumour microenvironment (TME) and impact immune responses in melanoma. She obtained her PhD from the University of Vienna in 2024. For her postdoctoral work Anais recently joined the lab of Dr. Susan M. Kaech at the Salk Institute in San Diego, USA, where she is investigating how anti-tumour immune responses are being established in glioblastoma.