A Serpin27A-dependent Toll Signaling Underlies Host Genetics of Cancer Resistance inDrosophila

Cancer resistance varies amongst individuals, although its host genetic underpinnings remain largely elusive. Remissions of sarcomas were first reported following repeated injections of patients with mixtures of killed bacteria—Coley’s toxins—a phenomenon, which was subsequently causally traced to induction of innate immunity. Here we reveal remission of Drosophila epithelial neoplasms by genetically triggered host innate immunity via Toll signaling. These neoplasms display capacities to receive and, in rare instances, induce Toll signaling. A tumor-induced and progressive Toll signaling, however, did not culminate in tumor suppression. By contrast, Drosophila hosts heterozygous for spn27A 1 mutation, which constitutively produce activated Toll ligand, Spz Act , displayed comprehensive tumor remission via Toll-induced, NF-κB-mediated, tumor cell death. Our results reveal a novel node of host genetic cancer resistance via serpin-dependent Toll signaling.