Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?
Immunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors developing innate or acquired resistance to checkpoint inhibition. Certain “hot” or “immune-sensitive” tumors become “cold”...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2142 |
| _version_ | 1797395730343657472 |
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| author | Rola El Sayed Yolla Haibe Ghid Amhaz Youssef Bouferraa Ali Shamseddine |
| author_facet | Rola El Sayed Yolla Haibe Ghid Amhaz Youssef Bouferraa Ali Shamseddine |
| author_sort | Rola El Sayed |
| collection | DOAJ |
| description | Immunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors developing innate or acquired resistance to checkpoint inhibition. Certain “hot” or “immune-sensitive” tumors become “cold” or “immune-resistant”, with resultant tumor growth and disease progression. Multiple factors are at play both at the cellular and host levels. The tumor microenvironment (TME) contributes the most to immune-resistance, with nutrient deficiency, hypoxia, acidity and different secreted inflammatory markers, all contributing to modulation of immune-metabolism and reprogramming of immune cells towards pro- or anti-inflammatory phenotypes. Both the tumor and surrounding immune cells require high amounts of glucose, amino acids and fatty acids to fulfill their energy demands. Thus, both compete over one pool of nutrients that falls short on needs, obliging cells to resort to alternative adaptive metabolic mechanisms that take part in shaping their inflammatory phenotypes. Aerobic or anaerobic glycolysis, oxidative phosphorylation, tryptophan catabolism, glutaminolysis, fatty acid synthesis or fatty acid oxidation, etc. are all mechanisms that contribute to immune modulation. Different pathways are triggered leading to genetic and epigenetic modulation with consequent reprogramming of immune cells such as T-cells (effector, memory or regulatory), tumor-associated macrophages (TAMs) (M1 or M2), natural killers (NK) cells (active or senescent), and dendritic cells (DC) (effector or tolerogenic), etc. Even host factors such as inflammatory conditions, obesity, caloric deficit, gender, infections, microbiota and smoking status, may be as well contributory to immune modulation, anti-tumor immunity and response to immune checkpoint inhibition. Given the complex and delicate metabolic networks within the tumor microenvironment controlling immune response, targeting key metabolic modulators may represent a valid therapeutic option to be combined with checkpoint inhibitors in an attempt to regain immune function. |
| first_indexed | 2024-03-09T00:39:51Z |
| format | Article |
| id | doaj.art-bc38ecf2fff84642af1c4f1412724b65 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:39:51Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc38ecf2fff84642af1c4f1412724b652023-12-11T17:54:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224214210.3390/ijms22042142Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?Rola El Sayed0Yolla Haibe1Ghid Amhaz2Youssef Bouferraa3Ali Shamseddine4Global Health Institute, American University of Beirut, Beirut 11-0236, LebanonDivision of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, LebanonDivision of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, LebanonDivision of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, LebanonDivision of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, LebanonImmunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors developing innate or acquired resistance to checkpoint inhibition. Certain “hot” or “immune-sensitive” tumors become “cold” or “immune-resistant”, with resultant tumor growth and disease progression. Multiple factors are at play both at the cellular and host levels. The tumor microenvironment (TME) contributes the most to immune-resistance, with nutrient deficiency, hypoxia, acidity and different secreted inflammatory markers, all contributing to modulation of immune-metabolism and reprogramming of immune cells towards pro- or anti-inflammatory phenotypes. Both the tumor and surrounding immune cells require high amounts of glucose, amino acids and fatty acids to fulfill their energy demands. Thus, both compete over one pool of nutrients that falls short on needs, obliging cells to resort to alternative adaptive metabolic mechanisms that take part in shaping their inflammatory phenotypes. Aerobic or anaerobic glycolysis, oxidative phosphorylation, tryptophan catabolism, glutaminolysis, fatty acid synthesis or fatty acid oxidation, etc. are all mechanisms that contribute to immune modulation. Different pathways are triggered leading to genetic and epigenetic modulation with consequent reprogramming of immune cells such as T-cells (effector, memory or regulatory), tumor-associated macrophages (TAMs) (M1 or M2), natural killers (NK) cells (active or senescent), and dendritic cells (DC) (effector or tolerogenic), etc. Even host factors such as inflammatory conditions, obesity, caloric deficit, gender, infections, microbiota and smoking status, may be as well contributory to immune modulation, anti-tumor immunity and response to immune checkpoint inhibition. Given the complex and delicate metabolic networks within the tumor microenvironment controlling immune response, targeting key metabolic modulators may represent a valid therapeutic option to be combined with checkpoint inhibitors in an attempt to regain immune function.https://www.mdpi.com/1422-0067/22/4/2142immunotherapycheckpoint inhibitorstumor microenvironmentimmune-metabolismglycolysisOXPHOS |
| spellingShingle | Rola El Sayed Yolla Haibe Ghid Amhaz Youssef Bouferraa Ali Shamseddine Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? International Journal of Molecular Sciences immunotherapy checkpoint inhibitors tumor microenvironment immune-metabolism glycolysis OXPHOS |
| title | Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? |
| title_full | Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? |
| title_fullStr | Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? |
| title_full_unstemmed | Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? |
| title_short | Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? |
| title_sort | metabolic factors affecting tumor immunogenicity what is happening at the cellular level |
| topic | immunotherapy checkpoint inhibitors tumor microenvironment immune-metabolism glycolysis OXPHOS |
| url | https://www.mdpi.com/1422-0067/22/4/2142 |
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