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Cells. 2019 May 11;8(5). pii: E445. doi: 10.3390/cells8050445.

Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity.

Author information

1
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. JAVIERFRANCISCO.MORA@ucr.ac.cr.
2
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Christina.Mertens@med.uni-heidelberg.de.
3
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. meier@biochem.uni-frankfurt.de.
4
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. fuhrmann@biochem.uni-frankfurt.de.
5
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. b.bruene@biochem.uni-frankfurt.de.
6
German Cancer Consortium (DKTK), Partner Site Frankfurt, Germany. b.bruene@biochem.uni-frankfurt.de.
7
Project Group Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology, 60596 Frankfurt, Germany. b.bruene@biochem.uni-frankfurt.de.
8
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. m.jung@biochem.uni-frankfurt.de.

Abstract

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.

KEYWORDS:

T cells; cancer cell metabolism; hypoxia; iron chelator; iron metabolism; tumor-associated macrophages

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