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 T helper cell type 2-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. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.

journal_name

J Leukoc Biol

authors

Cormier SA,Taranova AG,Bedient C,Nguyen T,Protheroe C,Pero R,Dimina D,Ochkur SI,O'Neill K,Colbert D,Lombari TR,Constant S,McGarry MP,Lee JJ,Lee NA

doi

10.1189/jlb.0106027

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

1131-9

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.0106027

journal_volume

79

pub_type

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