Themis Alissafi

Abstract Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA+ CAFs can form immunological synapses with Foxp3+ regulatory T cells (Tregs) in tumours.

Highlights • Intense metabolic reprogramming of Tregs occurs with autoimmunity • Treg mitochondrial oxidative stress is elevated during EAE • Treg mtROS attenuates lysosomal function, induces a DDR, and promotes cell death • mCAT overexpression prevents Treg death and restores autoimmune responses Summary Regulatory T cells (Tregs) are vital for the maintenance of immune homeostasis, while their dysfunction constitutes a cardinal feature of autoimmunity.

Themis Alissafi, Evangelia Kourepini, Davina C. M. Simoes, Nikolaos Paschalidis, Maria Aggelakopoulou, Tim Sparwasser, Louis Boon, Hamida Hammad, Bart N. Lambrecht and Vily Panoutsakopoulou J Immunol February 15, 2018, 200 (4) 1270-1282; DOI: https://doi.org/10.4049/jimmunol.1701345 Abstract In the context of inflammation, osteopontin (Opn) is known to promote effector responses, facilitating a proinflammatory environment; however, its role during antigenic tolerance induction is unknown.