IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid oxidation-dependent manner

Journal article


Publication Details

Author(s): Loschinski R, Böttcher M, Stoll A, Bruns H, Mackensen A, Mougiakakos D
Journal: Oncotarget
Publication year: 2018
Volume: 9
Journal issue: 17
Pages range: 13125-13138
ISSN: 1949-2553


Abstract

T-cell-based therapies represent a promising strategy for cancer treatment. In this context, cytokines are discussed as a bona fide instrument for fine-tuning T- cell biology. One promising candidate is the pleiotropic interleukin-21 (IL-21) with only little being known regarding its direct effects on human T-cells. Thus, we sought out to characterize the impact of IL-21 on T-cell metabolism, fitness, and differentiation. Culturing T-cells in presence of IL-21 elicited a metabolic skewing away from aerobic glycolysis towards fatty acid oxidation (FAO). These changes of the metabolic framework were paralleled by increased mitochondrial fitness and biogenesis. However, oxidative stress levels were not increased but rather decreased. Furthermore, elevated FAO and mitochondrial biomass together with enhanced antioxidative properties are linked to formation of longer lasting memory responses and less PD-1 expression. We similarly observed an IL-21-triggered induction of central memory-like T-cells and reduced levels of PD-1 on the cell surface. Taken together, IL-21 shifts T-cells towards an immunometabolic phenotype that has been associated with increased survivability and enhanced anti-tumor efficacy. In addition, our data reveals a novel interconnection between fatty acid metabolism and immune function regulated by IL 21.


FAU Authors / FAU Editors

Böttcher, Martin Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Bruns, Heiko PD Dr.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Böttcher-Loschinski, Romy Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Mackensen, Andreas Prof. Dr.
Lehrstuhl für Innere Medizin V
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie
Stoll, Andrej Dr. med.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie


How to cite

APA:
Loschinski, R., Böttcher, M., Stoll, A., Bruns, H., Mackensen, A., & Mougiakakos, D. (2018). IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid oxidation-dependent manner. Oncotarget, 9(17), 13125-13138. https://dx.doi.org/10.18632/oncotarget.24442

MLA:
Loschinski, Romy, et al. "IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid oxidation-dependent manner." Oncotarget 9.17 (2018): 13125-13138.

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Last updated on 2019-25-04 at 14:57