Publications by authors named "Robert Wiesheu"
Article Synopsis
- γδT cells are a type of immune cell that has gained attention for their potential in cancer immunotherapy, despite being understudied.
- Recent research shows that γδT cells play important roles in tumor development, growth, and spread, revealing complex behaviors that vary depending on the tissue and context.
- The article explores how different subsets of γδT cells are regulated, how they interact with cancer and other immune cells, and the significance of these findings for cancer patients.
In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αβ-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus.
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- γδ T cells play a crucial role in immune responses by quickly producing interferon-γ (IFN-γ), especially during the perinatal period when there's an increase in these cells that express CD8αβ heterodimers.
- Their development relies on low T cell receptor signaling, supported by interleukin (IL)-4 and IL-7, which helps regulate their growth.
- Aberrations in IL-7R-STAT5B signaling can lead to an excessive number of these cells in certain diseases, and they are also linked to pediatric cases of acute lymphoblastic leukemia.
Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs.
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- IL-17A-producing γδ T cells in mice mainly consist of two subclasses: Vγ6+ tissue-resident cells and Vγ4+ circulating cells, both of which show different characteristics in tumor conditions.
- Research using single-cell RNA sequencing revealed that Vγ6+ cells have high levels of PD-1, while Vγ4+ cells increase TIM-3 in response to specific tumor signals (IL-1β and IL-23).
- Blocking PD-1 or TIM-3 leads to an increase in these T cell populations in tumor-bearing mice, highlighting their role in developing resistance to immunotherapy in cancer therapies.
Article Synopsis
- - γδT cells are unique immune cells found in mucosal tissues that help monitor and maintain tissue health, as well as fight cancer by recognizing and killing stressed or cancerous cells via the NKG2D receptor.
- - Despite their known role in acting against tumors, new findings indicate that NKG2D actually regulates a group of γδT cells that promote tumor growth by producing IL-17A.
- - Research shows that removing the NKG2D gene reduces γδT cell levels in tumors and slows cancer progression, suggesting that in tumor environments with NKG2D ligands, these cells can accumulate and contribute to cancer advancement.
Unconventional T cells and their involvement in cancer are understudied in comparison to conventional T cells, but recent findings indicate that these cells play important roles in both cancer progression and inhibition. Here, we briefly review the dichotomous role of three unconventional T cell lineages: γδ T cells, MAIT cells and NKT cells. Studies using mouse models of cancer show how this unconventional trilogy interacts with cancer epithelial cells and other immune cell populations during tumour evolution.
View Article and Find Full Text PDFCurrent nutritional recommendations are focused on energy, fat, carbohydrate, protein and vitamins. Less attention has been paid to the nutritional demand of one-carbon units for nucleotide and methionine synthesis. Here, we investigated the impact of sodium formate supplementation as a nutritional intervention to increase the dietary intake of one-carbon units.
View Article and Find Full Text PDFMYC is implicated in the development and progression of pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumor development has been difficult to define. We used modestly elevated expression of human MYC, driven from the locus, to investigate the pancreatic phenotypes arising in mice from an approximation of trisomy. We show that this level of MYC alone suffices to drive pancreatic neuroendocrine tumors, and to accelerate progression of KRAS-initiated precursor lesions to metastatic pancreatic ductal adenocarcinoma (PDAC).
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