Zeaxanthin augments CD8 effector T cell function and immunotherapy efficacy.

The detailed mechanisms underlying the regulatory significance of dietary components in modulating anti-tumor immunity remain largely unknown. Here, we apply a co-culture-based screening approach using a blood nutrient compound library and identify zeaxanthin (ZEA), a dietary carotenoid pigment found in many fruits and vegetables and known for its role in eye health, as an immunomodulator that enhances the cytotoxicity of CD8 T cells against tumor cells. Oral supplementation with ZEA, but not its structural isomer lutein (LUT), enhances anti-tumor immunity in vivo.

Eating for immunity: how diet shapes our defenses.

Emerging studies on the diet-immune axis have uncovered novel dietary immune regulators and identified crucial targets and pathways mediating the crosstalk between specific dietary components and diverse immune cell populations. Here, we discuss the recent discovery and mechanisms by which diet-derived components, such as vitamins, amino acids, fatty acids, and antioxidants, could impact immune cell metabolism, alter signaling pathways, and reprogram the overall cellular responses. We also note crucial considerations that need to be tackled to make these findings clinically relevant, acknowledging that our current understanding often relies on simplified models that may not adequately represent the intricate network of factors influencing the diet-immune axis at the whole organism level.

NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth.

Unlabelled: Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1), a suppressor of the endoplasmic reticulum (ER) calcium channel protein inositol trisphosphate receptor (IP3R), is selectively upregulated and critical for cell proliferation and tumor growth potential of human NRAS-mutated melanoma, but not for melanoma expressing BRAF V600E.

Trans-vaccenic acid reprograms CD8 T cells and anti-tumour immunity.

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8 T cell function and anti-tumour immunity in vivo.

Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells.

Environmental stresses, including hypoxia or detachment for anchorage independence, or attenuation of mitochondrial respiration through inhibition of electron transport chain induce reductive carboxylation in cells with an enhanced fraction of citrate arising through reductive metabolism of glutamine. This metabolic process contributes to redox homeostasis and sustains biosynthesis of lipids. Reductive carboxylation is often dependent on cytosolic isocitrate dehydrogenase 1 (IDH1).

Syntrophic splitting of central carbon metabolism in host cells bearing functionally different symbiotic bacteria.

Insects feeding on the nutrient-poor diet of xylem plant sap generally bear two microbial symbionts that are localized to different organs (bacteriomes) and provide complementary sets of essential amino acids (EAAs). Here, we investigate the metabolic basis for the apparent paradox that xylem-feeding insects are under intense selection for metabolic efficiency but incur the cost of maintaining two symbionts for functions mediated by one symbiont in other associations. Using stable isotope analysis of central carbon metabolism and metabolic modeling, we provide evidence that the bacteriomes of the spittlebug Clastoptera proteus display high rates of aerobic glycolysis, with syntrophic splitting of glucose oxidation.

The Metabolome of Associations between Xylem-Feeding Insects and their Bacterial Symbionts.

Metabolomics has increasingly led to important insights in chemical ecology by identifying environmentally relevant small molecules that mediate inter-organismal interactions. Nevertheless, the application of metabolomics to investigate interactions between phytophagous insects and their microbial symbionts remains underutilized. Here, we investigated the metabolomes of the bacteriomes (organs bearing symbiotic bacteria) isolated from natural populations of five species of xylem-feeding insects.