Drosophila Sociality Influences Immune Peptide Load and Apoptosis-induced Tumor Suppression independently of the Antitumor Peptide Defensin

Abstract

Patients social environment might influence cancer outcome. This potentially happens in Drosophila, as we previously reported that the social context influences the growth of intestinal tumors. To uncover the underlying social-induced physiological mechanisms, we performed RNA-seq of isogenized beheaded tumorous Drosophila. Importantly, expression of several immune peptides varied according to the social-induced tumor growth effect. Furthermore, ectopic expression in tumors of the apoptotic-inhibitor p35 suppressed the social-induced effect. Next, we challenged the immune peptide Defensin, previously reported to suppress imaginal disc tumor growth through a cell-death/JNK-dependent network. Nonetheless, the social-induced tumor suppression was maintained upon Defensin overexpression or JNKK-knockdown in tumors, and in defensin mutants. Surprisingly, tumor growth was reduced in the latter, indicating that Defensin sustains the growth of these intestinal tumors. In summary, our study indicates that the social context affects the immune response and that a given immune peptide may have opposite effects depending on tumor type.