Expanding Spatial Metabolomics Coverage with Lithium-Doped Nanospray Desorption Electrospray Ionization Mass Spectrometry Imaging.

Spatial metabolomics has emerged as a powerful tool capable of revealing metabolic gradients throughout complex heterogeneous tissues. While mass spectrometry imaging (MSI) technologies designed to generate spatial metabolomic data have improved significantly over time, metabolite coverage is still a significant limitation. It is possible to achieve deeper metabolite coverage by imaging in positive and negative polarities or imaging several serial sections with different targeted biomolecular classes.

Metabolic engineering for optimized CAR-T cell therapy.

The broad effectiveness of T cell-based therapy for treating solid tumour cancers remains limited. This is partly due to the growing appreciation that immune cells must inhabit and traverse a metabolically demanding tumour environment. Accordingly, recent efforts have centred on using genome-editing technologies to augment T cell-mediated cytotoxicity by manipulating specific metabolic genes.

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites.

Autophagy metabolically suppresses CD8 T cell antitumor immunity.

Macroautophagy/autophagy is a critical regulator of adaptive T cell immunity and homeostasis. However, the role of T cell autophagy in regulating antitumor immune responses is less clear. In a recent study, we showed that deletion of the essential autophagy genes , or in host tissues dramatically impairs growth of autophagy-competent syngeneic tumors.

Autophagy Regulation of Metabolism Is Required for CD8 T Cell Anti-tumor Immunity.

Autophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8 T-cell-mediated control of tumors.