From tumor cell metabolism to tumor immune escape.Report as inadecuate

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* Corresponding author 1 INSERM U1040 Cellules souches normales et cancéreuses 2 Cellules souches normales et cancéreuses

Abstract : Tumorigenesis implies adaptation of tumor cells to an adverse environment. First, developing tumors must acquire nutrients to ensure their rapid growth. Second, they must escape the attack from the host immune system. Recent studies suggest that these phenomena could be related and that tumor cell metabolism may propel tumor immune escape. Tumor cell metabolism tends to avoid mitochondrial activity and oxidative phosphorylation OXPHOS, and largely relies on glycolysis to produce energy. This specific metabolism helps tumor cells to avoid the immune attack from the host by blocking or avoiding the immune attack. By changing their metabolism, tumor cells produce or sequester a variety of amino acids, lipids and chemical compounds that directly alter immune function therefore promoting immune evasion. A second group of metabolism-related modification targets the major histocompatibility complex-I MHC-I and related molecules. Tumor MHC-I presents tumor-associated antigens TAAs to cytotoxic T-cells CTLs and hence, sensitizes cancer cells to the cytolytic actions of the anti-tumor adaptive immune response. Blocking tumor mitochondrial activity decreases expression of MHC-I molecules at the tumor cell surface. And peroxynitrite PNT, produced by tumor-infiltrating myeloid cells, chemically modifies MHC-I avoiding TAA expression in the plasma membrane. These evidences on the role of tumor cell metabolism on tumor immune escape open the possibility of combining drugs designed to control tumor cell metabolism with new procedures of anti-tumor immunotherapy. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Keywords : Warburg effect cancer immunosurveillance cancer immunoediting MHC-1 OXPHOS

Author: Martin Villalba - Moeez Rathore - Nuria Lopez-Royuela - Ewelina Krzywinska - Johan Garaude - Nerea Allende-Vega -



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