Chaparro, J. | bioRxiv Science

bioRxiv2023

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma

Background/AimsEosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. MethodsEosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient ({Delta}dblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. ResultsActivated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (Ccl11-/- mice, {Delta}dblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. {Delta}dblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. ConclusionEosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

cancer biology↗

bioRxiv2020

Early metabolic priming under differing carbon sufficiency conditions influences peach fruit quality development

Crop load management is an important preharvest factor to balance yield, quality, and maturation in peach. However, few studies have addressed how preharvest factors impact metabolism on fruit of equal maturity. An experiment was conducted to understand how carbon competition impacts fruit internal quality and metabolism in Cresthaven peach trees by imposing distinct thinning severities. Fruit quality was evaluated at three developmental stages (S2, S3, S4), while controlling for equal maturity using non-destructive near-infrared spectroscopy. Non-targeted metabolite profiling was used to characterize fruit at each developmental stage from trees that were unthinned (carbon starvation) or thinned (carbon sufficiency). Carbon sufficiency resulted in significantly higher fruit dry matter content and soluble solids concentration at harvest when compared to the carbon starved, underscoring the true impact of carbon manipulation on fruit quality. Significant differences in the fruit metabolome between treatments were observed at S2 when phenotypes were similar, while less differences were observed at S4 when the carbon sufficient fruit exhibited a superior phenotype. This suggests a potential metabolic priming effect on fruit quality when carbon is sufficiently supplied during early fruit growth and development. In particular, elevated levels of catechin may suggest a link between secondary/primary metabolism and fruit quality development. HighlightAn investigation of variable carbon supply conditions in peach fruit reveals that early metabolic priming is associated with quality development

plant biology↗