Drosophila at the intersection of infection, inflammation, and cancer

Abstract

Recent studies show that both cellular and humoral aspects of innate immunity play important roles during tumor progression. These interactions have traditionally been explored in vertebrate model systems. In recent years, Drosophila has emerged as a genetically tractable model system for studying key aspects of tumorigenesis including proliferation, invasion, and metastasis. The absence of adaptive immunity in Drosophila provides a unique opportunity to study the interactions between innate immune system and cancer in different genetic contexts. In this review, I discuss recent advances made by using Drosophila models of cancer to study the role of innate immune pathways Toll/Imd, JNK, and JAK-STAT, microbial infection and inflammation during tumor progression.

Keywords: Drosophila; cancer; infection; inflammation; innate immune response.

Figure 1

Summary of tumor cell-immune system interactions in Drosophila. (A) Clones of cells defective for cell polarity genes such as scrib (green) generated in the context of a wild type tissue (yellow) are rapidly eliminated from the epithelium with the help of tumor associated hemocytes (TAHs, purple). (B) This antitumor immune response is subverted in scrib^−/− dRas1^V12 cells, leading to the establishment of an invasive tumor. (C) Reciprocal interactions between tumor cells (green) TAHs (purple), and fat body (gray) result in both local and systemic release of inflammatory cytokines in a positive feedback loop. (D) Microbial infection synergizes with dRas1^V12 to induce activation of JNK signaling (blue nuclei) and Mmp expression (red) in transformed hindgut epithelial cells, leading to migration and dissemination. (E) Microbial infection induces apoptosis of differentiated enterocytes (yellow), and synergizes with with dRas1^V12 to induce hyperplastic ISC/EB-like tumors. BM, Basement Membrane; Mmp, Matrix Metalloprotease; ISC, Intestinal Stem Cell; EB, Enteroblast.