The Immunometabolism Choreography

At Cell Metabolism, we often banter that “all roads lead to metabolism.” Over the years, we have witnessed the spectacular growth and integration of the metabolism field with other disciplines such as cancer biology, microbiology, and neurobiology. The field of immunometabolism is another example of interdisciplinary collaboration between the metabolism and immunology fields. While the concepts of inflammation as a driver of chronic metabolic diseases and of metabolic pathways supporting immune cell differentiation are more or less established, the idea that cellular metabolism affects immune function beyond ATP provision and redox balance is currently being actively pursued. As seen with cancer metabolism, there has been a shift in thinking away from metabolic cycles working as continuous loops and more toward them as dynamic modular components. In this Special Issue on immunometabolism, we chose to focus on a few of the key concepts currently shaping the field.In the opening Perspective of this series, Rathmell and colleagues highlight not only the many metabolic similarities but also critical differences between cancer and immune cells. They point out how these similarities and differences could potentially be exploited to treat cancer and immunological disorders. Next, Prochnicki and Latz turn their attention to a key signaling platform of the immune system, the inflammasome, and discuss how host- and microbial-derived metabolic cues regulate the inflammasome and how inflammasome-mediated metabolic sensing impacts diseases such as obesity, type 2 diabetes, and atherosclerosis. Restifo and colleagues then take us behind the scenes of T cell anti-tumor activity and propose strategies to harness metabolism for improved cancer immunotherapy. They postulate that it may be possible to establish a therapeutic window where metabolic inhibition does not compromise T cell function.On the theme of the gut microbiome, Ghosh and colleagues take stock of the complex interplay among the diverse metabolites produced by bacteria coming either from dietary components, from de novo synthesis, or through modification of existing metabolites in inflammatory diseases. Channeling Aesop, Pearce and colleagues highlight that, in metabolism, “where there is union there is strength” and provide an overview of ancillary pathways, such as those involved in the biosynthesis of polyamines, cholesterol, hexosamines, and nucleotides, which shape the complexity of the immune response. In closing, Netea and colleagues revisit fundamental concepts of myeloid cell metabolism during innate immune responses. They emphasize how different stimuli and/or tissue microenvironments will underlie heterogeneous metabolic response in myeloid cell activation and how a better integration of the molecular inflammatory response will pave the way to precision medicine.While much progress has undoubtedly been made, we are probably only just scratching the tip of the iceberg and foresee much more exciting biology coming on the immunometabolism horizon. The Special Issue cover art, designed by Ayaka Sugiura, pays tribute to the complex and stunning choreography between metabolism and immunology in achieving homeostatic balance; we eagerly await the next dance compositions of immunometabolism.