Publications by authors named "Frances Winkler"
The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.
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- Exhausted T cells, which are important for fighting viruses, are found in people with chronic hepatitis B and C infections.
- Researchers studied how metabolism affects these T cells by looking at samples from infected patients and using a mouse model.
- They found that different states of T cell exhaustion are linked to changes in their metabolism, and a protein called enolase plays a key role in regulating how well these T cells work.
Article Synopsis
- - The study explores how changes in the lipid composition of CD8 effector T cells influence their differentiation and signaling, specifically focusing on different types of phosphoinositides (PIP).
- - Naive T cells predominantly contain polyunsaturated PIP, which supports immediate signaling after T cell activation, while late T cells rely on saturated PIP for ongoing signaling due to decreased activity of the enzyme phospholipase C-γ1.
- - The research found that glucose is crucial for the production of saturated PIP, suggesting that different lipid profiles with distinct fatty acid compositions are critical for the successful functioning of T cells during their differentiation process.
Background & Aims: Despite recent translation of immunotherapies into clinical practice, the immunobiology of hepatocellular carcinoma (HCC), in particular the role and clinical relevance of exhausted and liver-resident T cells remain unclear. We therefore dissected the landscape of exhausted and resident T cell responses in the peripheral blood and tumor microenvironment of patients with HCC.
Methods: Lymphocytes were isolated from the blood, tumor and tumor-surrounding liver tissue of patients with HCC (n = 40, n = 10 treated with anti-PD-1 therapy).
Mass cytometry has become an important technique for the deep analysis of single cell protein expression required for precision systems immunology. The ability to profile more than 40 markers per cell is particularly relevant for the differentiation of cell types for which low parametric characterization has proven difficult, such as exhausted CD8 T cells (T). T with limited effector function accumulate in many chronic infections and cancers and are subject to inhibitory signaling mediated by several immune checkpoints (e.
View Article and Find Full Text PDFCompetition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth.
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