Ballesta-Illan, E. | Search bioRxiv

bioRxiv2026

Tumour rewires host tryptophan metabolism to promote organism-wide immune suppression

How tumour genotype reshapes systemic metabolism to drive immune tolerance and tumour progression remains unclear. Here, we show that Pten-deficient Drosophila tumours reprogram host tryptophan metabolism, triggering systemic and local changes in immune and stromal compartments to foster tolerance. Tumour-derived nitric oxide activates the kynurenine pathway in liver-like tissue, selectively increasing the 3-hydroxykynurenine (3-HK) branch. Host 3-HK promotes tumour progression and suppresses immune function via aryl hydrocarbon receptor (AhR) signalling. These results identify the kynurenine pathway as a central tumour-host nexus and reveal how tumour genotype creates immune vulnerabilities.

cancer biology↗

bioRxiv2018

The Notch and EGFR signaling regulate caspase inhibitor Diap1 to match supply with intestinal demand

The regenerative activity of adult stem cells carries a high risk of cancer, particularly in highly renewable tissues. To guarantee that the correct organ size is attained and to cope with the continual risk of cancer, developing tissues often use programmed cell death (PCD) as an adaptive mechanism to cull excess and abnormal cells. Members of the family of Inhibitor of Apoptosis Proteins (IAPs) inhibit caspases and cell death and are often overexpressed in cancer. Here, we show that Diap1 is expressed in committed progenitor (enteroblast) cells in the adult Drosophila intestine. Blocking endogenous caspases uncovered that more than half of enteroblasts produced by intestinal stem cells (ISCs) are actively eliminated by apoptosis in the physiological intestine and also led to tumorigenesis. We find that antagonistic interplay between the Notch and EGFR signaling on Diap1 regulation governs the enteroblast cell death or survival decision via the conserved Klumpfuss/WT1-Lozenge/RUNX axis, which also regulates of differentiation plasticity of enteroblasts. These data provide new insights into how apoptosis drives adult tissue renewal and protection against tumors.

cell biology↗