T cells

STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer

Adoptive cell therapy (ACT) can successfully treat hematopoietic cancers but lacks efficacy against solid tumors. This is due to insufficient T cell infiltration, high tumor heterogeneity, frequent antigen loss with subsequent tumor escape, and the immunosuppressive tumor microenvironment (TME). Alternative methods to boost the anticancer efficacy of adoptively transferred cells are actively pursued. Among adjuvants that are utilized to stimulate anticancer immune responses, ligands of the stimulator of interferon genes (STING) pathway have received increasing attention. STING activation can trigger dendritic cell (DC) activation and endogenous immune responses, thereby preventing tumor escape. Activation of the STING pathway in the context of ACT was accordingly associated with improved T cell trafficking and persistence in the TME combined with the reduced presence of immunosuppressive cells. Recent findings (…)

Fatty acids – from energy substrates to key regulators of cell survival, proliferation and effector function

Recent advances in immunology and cancer research show that fatty acids, their metabolism and their sensing have a crucial role in the biology of many different cell types. Indeed, they are able to affect cellular behaviour with great implications for pathophysiology. Both the catabolic and anabolic pathways of fatty acids present us with a number of enzymes, receptors and agonists/antagonists that are potential therapeutic targets, some of which have already been successfully pursued. Fatty acids can affect the differentiation of immune cells, particularly T cells, as well as their activation and function, with important consequences for the balance between anti- and pro-inflammatory signals in immune diseases, such as rheumatoid arthritis, psoriasis, diabetes, obesity and cardiovascular conditions. In the context of cancer biology, fatty acids mainly provide substrates for (…)

Regulation of T cell antitumor immune response by tumor induced metabolic stress

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.