Metabolic origins of spatial organization in the tumor microenvironment

Carmona‐Fontaine, Carlos; Deforet, Maxime; Akkari, Leila; Thompson, Craig B.; Joyce, Johanna A.; Xavier, João B.

doi:10.1073/pnas.1700600114

Cited by 270 publications

(267 citation statements)

References 63 publications

(112 reference statements)

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“…These features encompass the intrinsic metabolic properties of the cancer cells [4–6]. Clonal heterogeneity is further diversified through interactions with other cells types in the tumor and properties of the tumor microenvironment (TME), collectively referred to herein as extrinsically influencing variables [7–10]. Interactions among the intrinsic metabolic networks and the extrinsic effecters leads to a spectrum of cancer cells within a tumor that exhibit varying metabolic requirements and properties (Fig.…”

Section: Features Of the Tumor Microenvironment That Affect Metabolismmentioning

confidence: 99%

Metabolic Interactions in the Tumor Microenvironment

Lyssiotis

Kimmelman

2017

Trends in Cell Biology

630

500

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Tumors are dynamic pseudo-organs that contain numerous cell types interacting to create unique physiology. Within this network, the malignant cells encounter many challenges and rewire their metabolic properties accordingly. Such changes can be experienced and executed autonomously or through interaction with other cells in the tumor. The focus of this review is on the remodeling of the tumor microenvironment that leads to pathophysiologic interactions that are influenced and shaped by metabolism. They include symbiotic nutrient sharing, nutrient competition, and the role of metabolites as signaling molecules. Examples of such processes abound in normal organismal physiology, and such heterocelluar metabolic interactions are repurposed to support tumor metabolism and growth. The importance and ubiquity of these processes is just beginning to be realized, and insights into their role in tumor development and progression are being used to design new drug targets and cancer therapies.

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Section: Features Of the Tumor Microenvironment That Affect Metabolismmentioning

confidence: 99%

Metabolic Interactions in the Tumor Microenvironment

Lyssiotis

Kimmelman

2017

Trends in Cell Biology

630

500

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“…Therapies that result in lower tumor cell glucose consumption might work in part by altering environmental conditions within the tumor to better support TIL function (Chang et al, 2015). Similarly, the accumulation of metabolic products in the tumor microenvironment has important implications, such as the influence of high lactate concentration in tumors on macrophage polarization (Carmona-Fontaine et al, 2017; Colegio et al, 2014). Finally, immune cell function can also be limited by amino acid availability.…”

Section: Influence Of Available Nutrients On Immune Cell Metabolismmentioning

confidence: 99%

Biochemical Underpinnings of Immune Cell Metabolic Phenotypes

2017

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The metabolism of immune cells affects their function and influences host immunity. This review explores how immune cell metabolic phenotypes reflect biochemical dependencies, and highlights evidence that the metabolic state of immune cells and nutrient availability can both alter immune responses. The central importance of oxygen, energetics, and redox homeostasis in immune cell metabolism, and how these factors are reflected in different metabolic phenotypes, is also discussed. Linking immune cell metabolic phenotype to effector functions is important to understand how altering metabolism can impact the way in which immune cells meet their metabolic demands and affect the immune response in various disease contexts.

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“… demonstrated that lactate can induce a fraction of M2 gene expression, which was recently confirmed using global and pharmacological methods . Furthermore, hypoxia also influences M2‐associated gene expression , and more recently, Arg1 expression was concentrated in hypoxic regions of tumors, and inversely correlated with mannose receptor expression, another commonly used ‘marker’ of M2 macrophages . Arg1 expression in hypoxic zones is also observed in tuberculosis granulomas where it is required to suppress pathogenic T‐cell proliferation .…”

Section: Relationship Between the Environment Of Cancer And Myeloid Pmentioning

confidence: 76%

Nonresolving macrophage‐mediated inflammation in malignancy

Murray

2017

The FEBS Journal

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Tumors are populated with different cells of the immune system, each of which has the potential for pro-or antitumor functions. Macrophages are the numerically dominant type of myeloid cell in cancer and are suspected of having predominantly protumor functions. Key questions in cancer research concern the relationships between macrophages and anatomically different kinds of cancers, what specific properties of macrophages are involved in protumor functions and whether either macrophage numbers or functions can be modulated to enhance existing cancer therapies, for example, by reducing the immunosuppressive milieu such that anti-tumor T cells can provoke antitumor immunity. Accordingly, several antimacrophage preclinical modalities have been attempted and revealed substantial clinical barriers to their use. Therefore, understanding and targeting the specific pathways associated with protumor functions of macrophages, rather than macrophages themselves is a promising approach for both basic research and therapeutic development.

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Metabolic origins of spatial organization in the tumor microenvironment

Cited by 270 publications

References 63 publications

Metabolic Interactions in the Tumor Microenvironment

Metabolic Interactions in the Tumor Microenvironment

Biochemical Underpinnings of Immune Cell Metabolic Phenotypes

Nonresolving macrophage‐mediated inflammation in malignancy

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