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Full-Text Articles in Medicine and Health Sciences
Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias Schnell, Laurence Eisenlohr, Scott Waldman
Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias Schnell, Laurence Eisenlohr, Scott Waldman
Adam E Snook
Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory ā¦
Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman
Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman
Adam E Snook
The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2cā/ā) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous ā¦