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

Abstract

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals, however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4 + T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with Th2-dependent immune responses and that recruitment is a dynamic ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released 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. More importantly, these data also show that the mechanism(s) that elicits this host response occurs independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

“…In support of our study, one report described that eosinophil recruitment to tumor cells was an early event and independent of CD4 + T cells (38). Although different ways of inoculating tumor cells were employed, innate IL-5-producing non-T cells might also contribute to such early eosinophil regulation because IL-5 was upregulated immediately after tumor inoculation.…”

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

“…Even though the beneficial effect of TATE remains controversial, the presence of eosinophils appears as an indicator of good prognosis indicator in some cancers, such as head and neck cancers (7)(8)(9) and gastrointestinal cancers (10), particularly in colorectal cancers, in which high eosinophil counts were associated to increased 5-y survival (11). Clinical observations that eosinophil accumulation in intestinal tumors was associated to a better prognosis have been recently supported by experimental data in murine models (12)(13)(14).…”

Tumor stress, cell death and the ensuing immune response

“…65 DAMPs can promote the specific recruitment of eosinophil or neutrophil granulocytes into tumors. [66][67][68] Indeed, HMGB1 release could promote the infiltration of eosinophils into tumor tissue (reviewed in 66 ). Peripheral blood eosinophilia and tumor-associated tissue eosinophilia are associated with objective responses during immunotherapy with interleukin-2, IL-4, granulocyte-macrophage colony-stimulating factor, and anti CTLA-4.…”