The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression.
- S. Pushalkar, Mautin Hundeyin, G. Miller
- Biology, MedicineCancer Discovery
- 1 April 2018
It is found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy, and that the microbiome has potential as a therapeutic target in the modulation of disease progression.
The Necrosome Promotes Pancreas Oncogenesis via CXCL1 and Mincle Induced Immune Suppression
- Lena Seifert, G. Werba, G. Miller
- Biology, MedicineNature
- 11 February 2016
Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often…
TLR9 ligation in pancreatic stellate cells promotes tumorigenesis
- C. Zambirinis, E. Levie, G. Miller
- Biology, MedicineJournal of Experimental Medicine
- 26 October 2015
Zambirinis et al. show that TLR9 stimulation has a protumorigenic effect in pancreatic carcinoma by inducing pancreatic stellate cells to become fibrogenic and produce chemokines that stimulate…
Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.
- Lena Seifert, G. Werba, G. Miller
- Biology, MedicineGastroenterology
- 1 June 2016
Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses, allowing radiation to have increased efficacy in slowing tumor growth.
Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury
- M. Deutsch, C. Graffeo, G. Miller
- Biology, MedicineCell Death and Disease
- 1 May 2015
The fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3 is highlighted, suggesting that interference with distinct components of the necrosome must be considered separately.
Dectin-1 Activation on Macrophages by Galectin-9 Promotes Pancreatic Carcinoma and Peritumoral Immune-Tolerance
- D. Daley, Vishnu R Mani, G. Miller
- BiologyNature Network Boston
- 17 March 2017
It is found that dectin 1 can ligate the lectin galectin 9 in mouse and human PDA, which results in tolerogenic macrophage programming and adaptive immune suppression, and suggests that targeting dectIn 1 signaling is an attractive strategy for developing an immunotherapy for PDA.
NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma
- D. Daley, Vishnu R Mani, G. Miller
- Biology, MedicineJournal of Experimental Medicine
- 5 June 2017
It is found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA and pharmacological inhibition or deletion ofNLRP3, ASC, or caspase-1 protected against Pda and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME.
γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation
- D. Daley, C. Zambirinis, G. Miller
- BiologyCell
- 8 September 2016
TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia
- S. Greco, L. Tomkötter, G. Miller
- Biology, MedicinePLoS ONE
- 14 July 2015
It is shown that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival and other immunotherapeutic strategies were not effective.
Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma
- R. Barilla, B. Diskin, G. Miller
- BiologyNature Communications
- 29 March 2019
The authors show that specialized subsets of tumour-infiltrating dendritic cells induce distinct CD4+ T cell programs and specifically identify a CD103–CD11b+ subset which induces tumor-promoting FoxP3– Type-1 regulatory T cells.
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