Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment
The tumor microenvironment (TME) is a complex and constantly changing cellular system composed of heterogeneous populations of tumor cells and non-transformed stromal cells, such as stem cells, fibroblasts, endothelial cells, pericytes, adipocytes, and innate and adaptive immune cells. Tumor, stroma...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1101503/full |
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| author | Jesus J. Benito-Lopez Jesus J. Benito-Lopez Mario Marroquin-Muciño Mario Marroquin-Muciño Mario Perez-Medina Mario Perez-Medina Rodolfo Chavez-Dominguez Rodolfo Chavez-Dominguez Dolores Aguilar-Cazares Miriam Galicia-Velasco Jose S. Lopez-Gonzalez |
| author_facet | Jesus J. Benito-Lopez Jesus J. Benito-Lopez Mario Marroquin-Muciño Mario Marroquin-Muciño Mario Perez-Medina Mario Perez-Medina Rodolfo Chavez-Dominguez Rodolfo Chavez-Dominguez Dolores Aguilar-Cazares Miriam Galicia-Velasco Jose S. Lopez-Gonzalez |
| author_sort | Jesus J. Benito-Lopez |
| collection | DOAJ |
| description | The tumor microenvironment (TME) is a complex and constantly changing cellular system composed of heterogeneous populations of tumor cells and non-transformed stromal cells, such as stem cells, fibroblasts, endothelial cells, pericytes, adipocytes, and innate and adaptive immune cells. Tumor, stromal, and immune cells consume available nutrients to sustain their proliferation and effector functions and, as a result of their metabolism, produce a wide array of by-products that gradually alter the composition of the milieu. The resulting depletion of essential nutrients and enrichment of by-products work together with other features of the hostile TME to inhibit the antitumor functions of immune cells and skew their phenotype to promote tumor progression. This review briefly describes the participation of the innate and adaptive immune cells in recognizing and eliminating tumor cells and how the gradual metabolic changes in the TME alter their antitumor functions. In addition, we discuss the overexpression of the immune checkpoints and their ligands as a result of nutrient deprivation and by-products accumulation, as well as the amplification of the metabolic alterations induced by the immune checkpoints, which creates an immunosuppressive feedback loop in the TME. Finally, the combination of metabolic and immune checkpoint inhibitors as a potential strategy to treat cancer and enhance the outcome of patients is highlighted. |
| first_indexed | 2024-04-10T23:32:23Z |
| format | Article |
| id | doaj.art-f8ce755566724932ba43acc6cee795d1 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T23:32:23Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f8ce755566724932ba43acc6cee795d12023-01-12T05:10:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.11015031101503Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironmentJesus J. Benito-Lopez0Jesus J. Benito-Lopez1Mario Marroquin-Muciño2Mario Marroquin-Muciño3Mario Perez-Medina4Mario Perez-Medina5Rodolfo Chavez-Dominguez6Rodolfo Chavez-Dominguez7Dolores Aguilar-Cazares8Miriam Galicia-Velasco9Jose S. Lopez-Gonzalez10Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoPosgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoLaboratorio de Quimioterapia Experimental, Departamento de Bioquimica, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoLaboratorio de Quimioterapia Experimental, Departamento de Bioquimica, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoPosgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoLaboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, MexicoThe tumor microenvironment (TME) is a complex and constantly changing cellular system composed of heterogeneous populations of tumor cells and non-transformed stromal cells, such as stem cells, fibroblasts, endothelial cells, pericytes, adipocytes, and innate and adaptive immune cells. Tumor, stromal, and immune cells consume available nutrients to sustain their proliferation and effector functions and, as a result of their metabolism, produce a wide array of by-products that gradually alter the composition of the milieu. The resulting depletion of essential nutrients and enrichment of by-products work together with other features of the hostile TME to inhibit the antitumor functions of immune cells and skew their phenotype to promote tumor progression. This review briefly describes the participation of the innate and adaptive immune cells in recognizing and eliminating tumor cells and how the gradual metabolic changes in the TME alter their antitumor functions. In addition, we discuss the overexpression of the immune checkpoints and their ligands as a result of nutrient deprivation and by-products accumulation, as well as the amplification of the metabolic alterations induced by the immune checkpoints, which creates an immunosuppressive feedback loop in the TME. Finally, the combination of metabolic and immune checkpoint inhibitors as a potential strategy to treat cancer and enhance the outcome of patients is highlighted.https://www.frontiersin.org/articles/10.3389/fonc.2022.1101503/fulltumor microenvironmentmetabolic reprogrammingimmune cellstumor cellsglucose and lactateexogen amino acids |
| spellingShingle | Jesus J. Benito-Lopez Jesus J. Benito-Lopez Mario Marroquin-Muciño Mario Marroquin-Muciño Mario Perez-Medina Mario Perez-Medina Rodolfo Chavez-Dominguez Rodolfo Chavez-Dominguez Dolores Aguilar-Cazares Miriam Galicia-Velasco Jose S. Lopez-Gonzalez Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment Frontiers in Oncology tumor microenvironment metabolic reprogramming immune cells tumor cells glucose and lactate exogen amino acids |
| title | Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| title_full | Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| title_fullStr | Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| title_full_unstemmed | Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| title_short | Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| title_sort | partners in crime the feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment |
| topic | tumor microenvironment metabolic reprogramming immune cells tumor cells glucose and lactate exogen amino acids |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1101503/full |
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