title: γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation.
abstract: Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αβT cells. Although αβT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Donnele
authors: D
authors: Daley
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Constantinos Pantelis
authors: CP
authors: Zambirinis
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Lena
authors: L
authors: Seifert
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Neha
authors: N
authors: Akkad
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Navyatha
authors: N
authors: Mohan
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Gregor
authors: G
authors: Werba
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Rocky
authors: R
authors: Barilla
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Alejandro
authors: A
authors: Torres-Hernandez
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Mautin
authors: M
authors: Hundeyin
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Vishnu Raj Kumar
authors: VRK
authors: Mani
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Antonina
authors: A
authors: Avanzi
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Daniel
authors: D
authors: Tippens
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Rajkishen
authors: R
authors: Narayanan
authors: Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Jung-Eun
authors: JE
authors: Jang
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Elliot
authors: E
authors: Newman
authors: Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
authors: Venu Gopal
authors: VG
authors: Pillarisetty
authors: Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington Oxford OX3 7FY, UK.
authors: Michael Loran
authors: ML
authors: Dustin
authors: Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Dafna
authors: D
authors: Bar-Sagi
authors: Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
authors: Cristina
authors: C
authors: Hajdu
authors: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA. Electronic address: george.miller@nyumc.org.
authors: George
authors: G
authors: Miller
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D063646:Carcinogenesis / Q000276:immunology* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology* / Q000503:physiopathology*; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018925:Chemokines; D008024:Ligands
keywords: Kras; cancer; checkpoint ligands