Pivotal Advance : Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details sur- rounding this eosinophilia remain largely unde- fined and anecdotal. We used a B16-F10 mela- noma cell injection model to demonstrate that eo- sinophil infiltration of tumors occurred from the earliest palpable stages with significant accumula- tions only in the necrotic and capsule regions. Fur- thermore, the presence of diffuse extracellular ma- trix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicat- ing that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4 T cells and adoptive transfer of eosinophils sug- gested, respectively, that the accumulation of eo- sinophils is not associated with T helper cell type 2-dependent immune responses and that recruit- ment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration stud- ies have identified what appears to be a novel che- motactic factor(s) released by stressed/dying mela- noma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) re- leased from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of im- mune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis. J. Leukoc. Biol. 79: 000-000; 2006.