The association between cancers and inflammation is well established, with the first known correlation made by Rudolph Virchow in the 19th century. Recent clinical evidence supports a role for immunity in cancer suppression. For example, transplant recipients, who receive immunosuppressants to avoid rejection, have a higher incidence of cancer, and the presence of lymphocytes in colorectal tumors is associated with greater patient survival. Both adaptive and innate immune systems respond to cancer. The adaptive immune system recognizes tumor-specific antigens, while the innate system participates in the initial tumor response, similar to the inflammatory response to wounds. The mechanisms underlying innate immune recognition and response to tumors are unknown. It has been suggested that the innate response to tumors could be triggered by ‘danger signals’ sent by damaged tissue. Better understanding of this first line of anti-cancer defense may provide novel therapeutic options.

Here, the fruit fly is used to define the innate immune response induced by the presence of a tumor. Circulating immune cells, called hemocytes, increased their number in response to the tumor and adhered to its surface, inhibiting tumor growth. Different tumor-derived stimuli triggered hemocytes to either proliferate or adhere to the tumor surface, similar to the immune response triggered by aseptic wounds. Hemocyte proliferation was induced by tumor-, fat body- and hemocyte-derived cytokines that activate JAK/STAT signaling, and hemocyte adhesion was a consequence of breaks in the tumor basement membrane (BM).

This study defines how the fly innate immune system recognizes and reacts to tumors. The components described here in the fly are well conserved in mammals, including JAK/STAT cytokine signaling, JNK-mediated stress signaling, and constituents of the BM. Thus, the fly should provide a genetically tractable model for the study and discovery of components involved in the response to tumors and tissue damage, which could have broad implications for our understanding of normal and aberrant self-recognition.

2008