Spatial Immunometabolism: Integrating Technologies to Decode Cellular Metabolism in Tissues

TL;DR

This paper reviews new technologies that allow scientists to study how immune cell metabolism is influenced by their surrounding tissue environment, especially in cancer.

Contribution

The paper introduces the concept of spatial immunometabolism and emphasizes the integration of multimodal technologies to study immune metabolism in tissue context.

Findings

Technologies like mass spectrometry imaging and vibrational microscopy enable spatially resolved analysis of immune metabolism.

Integrating transcriptomic, proteomic, and spatial data reveals how metabolic organization affects immune function in cancer.

Spatial immunometabolism offers new insights into immune regulation in health and disease.

Abstract

The metabolic programs of immune cells influence their activation, differentiation, and effector functions. While much of immunometabolism has focused on cell‐intrinsic regulation, it is now clear that metabolic activity is profoundly influenced by the surrounding tissue environment. In tumors and other inflammatory settings, immune cells are shaped by nutrient gradients, hypoxia, and immunoregulatory metabolites, factors that are spatially heterogeneous and often poorly captured by traditional methods. This review highlights recent technological advances that enable spatially resolved analysis of immune metabolism, with an emphasis on multimodal integration and cancer as a model system. Mass spectrometry imaging (MALDI, DESI), high‐resolution platforms like SIMS, and vibrational imaging approaches such as Raman microscopy enable direct visualization of metabolites in tissue. Transcriptomic and proteomic data can be used to infer metabolic states, and computational models are being developed to integrate these diverse data layers. Together, these technologies are transforming the study of immunometabolism from dissociated cells to the intact tissue context. Key challenges remain in resolution, annotation, and data integration, but spatial immunometabolism holds particular promise for illuminating mechanisms of immune regulation in health and disease.

This review highlights recent advances that enable spatially resolved analysis of immunometabolism within tissue microenvironments. Integrating mass spectrometry imaging, vibrational microscopy, and spatial omics reveals how metabolic organization shapes immune function in cancer and other pathologies.

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