The inhibitory T-cell receptor PD1 dampens T-cell responses, and is therefore a major target of cancer immunotherapy, which aims to strengthen T-cell dependent anti-tumor immune responses.
In a new study published in Blood Advances, Daniela Chmiest and colleagues from the lab of Margot Thome-Miazza uncover how PD1 inhibits T-cell activation by impairing the formation of the immune synapse, the major contact zone between T-cells and tumor cells. The researchers identified multiple cytoskeleton proteins that are affected by PD1, likely causing an impaired formation of the T-cell – tumor cell contact zone. Together with the team of Laurence de Leval (CHUV), the researchers further identified a T-cell cytoskeleton compound, Vimentin, that is altered in patient tumor tissues that are infiltrated by PD1-positive T cells. These results broaden our understanding of the function of PD1 and suggest that a specific alteration (a lack of phosphorylation) of Vimentin could be used as a biomarker for patients that might benefit from an anti-PD1 cancer immunotherapy.
Link to the paper : https://doi.org/10.1182/bloodadvances.2023011901