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Cassim, S., & Pouyssegur, J. (2020). Tumor Microenvironment: A Metabolic Player that Shapes the Immune Response. International Journal of Molecular Sciences, 21(1). Added by: Dr. Enrique Feoli (10/10/2020, 18:28) Last edited by: Dr. Enrique Feoli (10/10/2020, 18:39) |
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| Resource type: Journal Article DOI: 10.3390/ijms21010157 BibTeX citation key: Cassim2020 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Redox microenvironment Creators: Cassim, Pouyssegur Collection: International Journal of Molecular Sciences |
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| Abstract |
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Immune cells survey and patrol throughout the body and sometimes take residence in niche environments with distinct cellular subtypes and nutrients that may fluctuate from those in which they matured. Rooted in immune cell physiology are metabolic pathways and metabolites that not only deliver substrates and energy for growth and survival, but also instruct effector functions and cell differentiation. Unlike cancer cells, immune cells are not subject to a “Darwinian evolutionary pressure” that would allow them to adapt to developing tumors but are often irrevocably affected to local nutrient deprivation. Thus, immune cells must metabolically adapt to these changing conditions in order to perform their necessary functions. On the other hand, there is now a growing appreciation that metabolic changes occurring in cancer cells can impact on immune cell functionality and contribute to tumor immune evasion, and as such, there is a considerable and growing interest in developing techniques that target metabolism for immunotherapy. In this review, we discuss the metabolic plasticity displayed by innate and adaptive immune cells and highlight how tumor-derived lactate and tumor acidity restrict immunity. To our knowledge, this review outlines the most recent insights on how tumor microenvironment metabolically instructs immune responsiveness.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Notes |
Metabolic competition in the tumor microenvironment is a driver of T cell responsiveness. As mentioned in the review’s text, the increased metabolism displayed by tumor cells consumes most nutrients from the surrounding microenvironment, and as a consequence, impacts on the intrinsic metabolism of T cells, with a decreased ability to produce cytokines (especially IFN-γ) and to develop into tumor-specific T effector cells, leading to T cell hypo-responsiveness and increased tumor progression (nutrient-restricted T cells in red). Conversely, in a nutrient-enriched microenvironment, T cell metabolism increases (glycolysis) and leads to an improved IFN-γ production and immune response (T cells nutrient sufficient in green). IFN-γ: Interferon gamma. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |