Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity
The inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, inc...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/5/445 |
| _version_ | 1797722814790238208 |
|---|---|
| author | Javier Mora Christina Mertens Julia K. Meier Dominik C. Fuhrmann Bernhard Brüne Michaela Jung |
| author_facet | Javier Mora Christina Mertens Julia K. Meier Dominik C. Fuhrmann Bernhard Brüne Michaela Jung |
| author_sort | Javier Mora |
| collection | DOAJ |
| description | The inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, including myeloid cells and lymphocytes, acquire a tumor-supportive, anti-inflammatory phenotype due to their interaction with tumor cells. Microenvironmental cues such as inflammation and hypoxia are mainly responsible for creating a tumor-supportive niche. Moreover, it is becoming apparent that the availability of iron within the tumor not only affects tumor growth and survival, but also the polarization of infiltrating immune cells. The interaction of tumor cells and infiltrating immune cells is multifaceted and complex, finally leading to different activation phenotypes of infiltrating immune cells regarding their functional heterogeneity and plasticity. In recent years, it was discovered that these phenotypes are mainly implicated in defining tumor outcome. Here, we discuss the role of the metabolic activation of both tumor cells and infiltrating immune cells in order to adapt their metabolism during tumor growth. Additionally, we address the role of iron availability and the hypoxic conditioning of the tumor with regard to tumor growth and we describe the relevance of therapeutic strategies to target such metabolic characteristics. |
| first_indexed | 2024-03-12T09:54:10Z |
| format | Article |
| id | doaj.art-0c647a007089410e8715d3aee0c8408d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:54:10Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0c647a007089410e8715d3aee0c8408d2023-09-02T12:19:13ZengMDPI AGCells2073-44092019-05-018544510.3390/cells8050445cells8050445Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive ImmunityJavier Mora0Christina Mertens1Julia K. Meier2Dominik C. Fuhrmann3Bernhard Brüne4Michaela Jung5Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyThe inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, including myeloid cells and lymphocytes, acquire a tumor-supportive, anti-inflammatory phenotype due to their interaction with tumor cells. Microenvironmental cues such as inflammation and hypoxia are mainly responsible for creating a tumor-supportive niche. Moreover, it is becoming apparent that the availability of iron within the tumor not only affects tumor growth and survival, but also the polarization of infiltrating immune cells. The interaction of tumor cells and infiltrating immune cells is multifaceted and complex, finally leading to different activation phenotypes of infiltrating immune cells regarding their functional heterogeneity and plasticity. In recent years, it was discovered that these phenotypes are mainly implicated in defining tumor outcome. Here, we discuss the role of the metabolic activation of both tumor cells and infiltrating immune cells in order to adapt their metabolism during tumor growth. Additionally, we address the role of iron availability and the hypoxic conditioning of the tumor with regard to tumor growth and we describe the relevance of therapeutic strategies to target such metabolic characteristics.https://www.mdpi.com/2073-4409/8/5/445tumor-associated macrophagesT cellshypoxiacancer cell metabolismiron metabolismiron chelator |
| spellingShingle | Javier Mora Christina Mertens Julia K. Meier Dominik C. Fuhrmann Bernhard Brüne Michaela Jung Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity Cells tumor-associated macrophages T cells hypoxia cancer cell metabolism iron metabolism iron chelator |
| title | Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity |
| title_full | Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity |
| title_fullStr | Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity |
| title_full_unstemmed | Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity |
| title_short | Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity |
| title_sort | strategies to interfere with tumor metabolism through the interplay of innate and adaptive immunity |
| topic | tumor-associated macrophages T cells hypoxia cancer cell metabolism iron metabolism iron chelator |
| url | https://www.mdpi.com/2073-4409/8/5/445 |
| work_keys_str_mv | AT javiermora strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity AT christinamertens strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity AT juliakmeier strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity AT dominikcfuhrmann strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity AT bernhardbrune strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity AT michaelajung strategiestointerferewithtumormetabolismthroughtheinterplayofinnateandadaptiveimmunity |