Microenvironment-Dependent Gradient of CTL Exhaustion in the AE17sOVA Murine Mesothelioma Tumor Model
| Autor: | Christopher J Stairiker, Delia J. Nelson, Panagiota I. Spantidea, Yvonne M. Mueller, Joachim G.J.V. Aerts, Linda M. Bradley, Inge Brouwers-Haspels, Jennifer L. Hope, Marjan van Meurs, Caoimhe H. Kiernan, Peter D. Katsikis, Laurine C Rijsbergen |
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| Přispěvatelé: | Immunology, Pulmonary Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Mesothelioma
0301 basic medicine tumors lcsh:Immunologic diseases. Allergy T cell Immunology chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Lymphocyte Activation CD8+ T cells Mice 03 medical and health sciences 0302 clinical medicine Immune system Tumor Microenvironment medicine Animals Immunology and Allergy Cytotoxic T cell cancer Cells Cultured Original Research T cell exhaustion business.industry peripheral lymphoid organs Blockade Mice Inbred C57BL Disease Models Animal CTL 030104 developmental biology medicine.anatomical_structure Tumor progression Cancer cell Cancer research Female Immunotherapy business lcsh:RC581-607 CD8 T-Lymphocytes Cytotoxic 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 10 (2020) Frontiers in Immunology, 10:3074. Frontiers Media S.A. Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | The immune system, and in particular, cytotoxic CD8+ T cells (CTLs), plays a vital part in the prevention and elimination of tumors. In many patients, however, CTL-mediated tumor killing ultimately fails in the clearance of cancer cells resulting in disease progression, in large part due to the progression of effector CTL into exhausted CTL. While there have been major breakthroughs in the development of CTL-mediated “reinvigoration”-driven immunotherapies such as checkpoint blockade therapy, there remains a need to better understand the drivers behind the development of T cell exhaustion. Our study highlights the unique differences in T cell exhaustion development in tumor-specific CTL which arises over time in a mouse model of mesothelioma. Importantly, we also show that peripheral tumor-specific T cells have a unique expression profile compared to exhausted tumor-infiltrating CTL at a late-stage of tumor progression in mice. Together, these data suggest that greater emphasis should be placed on understanding contributions of individual microenvironments in the development of T cell exhaustion. |
| Databáze: | OpenAIRE |
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