Browsing by Author "Liria, Miguel"
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Item Open Access BTLA+CD200+ B cells dictate the divergent immune landscape and immunotherapeutic resistance in metastatic vs. primary pancreatic cancer(Oncogene, 2022-09-16) Diskin, Brian; Adam, Salma; Soto, Gustavo Sanchez; Liria, Miguel; Aykut, Berk; Sundberg, Belen; Li, Eric; Leinwand, Joshua; Chen, Ruonan; Kim, Mirhee; Salas, Ruben D; Cassini, Marcelo F; Buttar, Chandan; Wang, Wei; Farooq, Mohammad Saad; Shadaloey, Sorin AA; Werba, Gregor; Fnu, Amreek; Yang, Fan; Hirsch, Carolina; Glinski, John; Panjwani, Angilee; Weitzner, Yael; Cohen, Deirdre; Asghar, Usman; Miller, GeorgeItem Open Access PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer(Nature Immunology, 2020-04) Diskin, Brian; Adam, Salma; Cassini, Marcelo F; Sanchez, Gustavo; Liria, Miguel; Aykut, Berk; Buttar, Chandan; Li, Eric; Sundberg, Belen; Salas, Ruben D; Chen, Ruonan; Wang, Junjie; Kim, Mirhee; Farooq, Mohammad Saad; Nguy, Susanna; Fedele, Carmine; Tang, Kwan Ho; Chen, Ting; Wang, Wei; Hundeyin, Mautin; Rossi, Juan A Kochen; Kurz, Emma; Haq, Muhammad Israr Ul; Karlen, Jason; Kruger, Emma; Sekendiz, Zennur; Wu, Dongling; Shadaloey, Sorin AA; Baptiste, Gillian; Werba, Gregor; Selvaraj, Shanmugapriya; Loomis, Cynthia; Wong, Kwok-Kin; Leinwand, Joshua; Miller, GeorgeItem Open Access Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma(Nature Communications) Barilla, Rocky M; Diskin, Brian; Caso, Raul Caso; Lee, Ki Buom; Mohan, Navyatha; Buttar, Chandan; Adam, Salma; Sekendiz, Zennur; Wang, Junjie; Salas, Ruben D; Cassini, Marcelo F; Karlen, Jason; Sundberg, Belen; Akbar, Hashem; Levchenko, Dmitry; Gakhal, Inderdeep; Gutierrez, Johana; Wang, Wei; Hundeyin, Mautin; Torres-Hernandez, Alejandro; Leinwand, Joshua; Kurz, Emma; Rossi, Juan A Kochen; Mishra, Ankita; Liria, Miguel; Sanchez, Gustavo; Panta, Jyoti; Loke, P’ng; Aykut, Berk; Miller, GeorgeAbstractThe drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103− DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103− DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.Item Open Access γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming(Hepatology, 2020-02) Torres‐Hernandez, Alejandro; Wang, Wei; Nikiforov, Yuri; Tejada, Karla; Torres, Luisana; Kalabin, Aleksandr; Adam, Salma; Wu, Jingjing; Lu, Lu; Chen, Ruonan; Lemmer, Aaron; Camargo, Jimmy; Hundeyin, Mautin; Diskin, Brian; Aykut, Berk; Kurz, Emma; Kochen Rossi, Juan A; Khan, Mohammed; Liria, Miguel; Sanchez, Gustavo; Wu, Nan; Su, Wenyu; Adams, Steven; Haq, Muhammad Israr Ul; Farooq, Mohammad Saad; Vasudevaraja, Varshini; Leinwand, Joshua; Miller, GeorgeBackground and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4+, PD1+, Ly6C+CD44+ phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4+ T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.