title: 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.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
authors.forename: Anna G
authors.initials: AG
authors.lastname: Taranova
authors.forename: Carrie
authors.initials: C
authors.lastname: Bedient
authors.forename: Thanh
authors.initials: T
authors.lastname: Nguyen
authors.forename: Cheryl
authors.initials: C
authors.lastname: Protheroe
authors.forename: Ralph
authors.initials: R
authors.lastname: Pero
authors.forename: Dawn
authors.initials: D
authors.lastname: Dimina
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.forename: Katie
authors.initials: K
authors.lastname: O'Neill
authors.forename: Dana
authors.initials: D
authors.lastname: Colbert
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Lombari
authors.forename: Stephanie
authors.initials: S
authors.lastname: Constant
authors.forename: Michael P
authors.initials: MP
authors.lastname: McGarry
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004802:Eosinophilia / Q000209:etiology / Q000503:physiopathology; D004804:Eosinophils / Q000276:immunology* / Q000637:transplantation; D007157:Immunologic Surveillance; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007279:Injections, Subcutaneous; D015848:Interleukin-5 / Q000235:genetics; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009336:Necrosis; D009368:Neoplasm Transplantation; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D015848:Interleukin-5