Transcriptomic analysis of NICD overexpression in salivary gland imaginal ring tumors and tumor-bearing hosts

In this study, using a Drosophila tumor transplantation model, we found that the innate immune response, initiated by translocated commensal bacteria from a compromised intestine, significantly contributes to reduced lifespan in tumor hosts. Our data identify the renal system as a central hub of this paraneoplastic syndrome model, wherein the pericardial nephrocytes undergo severe damage due to an elevated immune response triggered by gut dysbiosis and bacterial translocation. This innate immune response-induced nephrocyte damage is a major contributor to reduced lifespan in the tumor hosts, as demonstrated by our findings that blocking the NF-kB/Imd pathway in nephrocytes or removing gut bacteria via germ-free derivation or antibiotic treatment ameliorates nephrocyte deterioration and extends the lifespan of tumor hosts. Treatment with a detoxifying drug also extended the life span of the tumor hosts. Our findings highlight the critical role of the gut-kidney axis in the paraneoplastic complications observed in cancer-bearing flies, suggesting potential therapeutic targets for mitigating similar complications in cancer patients.