Interleukin-35 Limits Anti-Tumor Immunity
| Autor: | Meghan E. Turnis, Hiroshi Yano, Lawrence P. Andrews, Amy J. Beres, Deepali V. Sawant, Creg J. Workman, Dario A. A. Vignali, Greg M. Delgoffe, Andrea L. Szymczak-Workman, Peter Vogel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Skin Neoplasms LAG3 medicine.medical_treatment Programmed Cell Death 1 Receptor Immunology Melanoma Experimental chemical and pharmacologic phenomena Cell Growth Processes T-Lymphocytes Regulatory Article Mice 03 medical and health sciences 0302 clinical medicine Antigens CD Immunity Cell Line Tumor Tumor Microenvironment medicine Animals Humans Immunology and Allergy Antibodies Blocking Hepatitis A Virus Cellular Receptor 2 Cell Proliferation Mice Knockout Tumor microenvironment biology Antitumor immunity Effector Interleukins Lymphocyte Activation Gene 3 Protein Tumor Burden Mice Inbred C57BL 030104 developmental biology Infectious Diseases Cytokine 030220 oncology & carcinogenesis Interleukin 35 biology.protein Receptors Virus Antibody Immunologic Memory |
| Zdroj: | Immunity. 44:316-329 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2016.01.013 |
| Popis: | Summary Regulatory T (Treg) cells pose a major barrier to effective anti-tumor immunity. Although Treg cell depletion enhances tumor rejection, the ensuing autoimmune sequelae limits its utility in the clinic and highlights the need for limiting Treg cell activity within the tumor microenvironment. Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function. Using an IL-35 reporter mouse, we observed substantial enrichment of IL-35 + Treg cells in tumors. Neutralization with an IL-35-specific antibody or Treg cell-restricted deletion of IL-35 production limited tumor growth in multiple murine models of human cancer. Limiting intratumoral IL-35 enhanced T cell proliferation, effector function, antigen-specific responses, and long-term T cell memory. Treg cell-derived IL-35 promoted the expression of multiple inhibitory receptors (PD1, TIM3, LAG3), thereby facilitating intratumoral T cell exhaustion. These findings reveal previously unappreciated roles for IL-35 in limiting anti-tumor immunity and contributing to T cell dysfunction in the tumor microenvironment. |
| Databáze: | OpenAIRE |
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