Cormier Stephania A, Taranova Anna G, Bedient Carrie, Nguyen Thanh, Protheroe Cheryl, Pero Ralph, Dimina Dawn, Ochkur Sergei I, O'Neill Katie, Colbert Dana, Lombari Theresa R, Constant Stephanie, McGarry Michael P, Lee James J, Lee Nancy A
Division of Hematology and Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
J Leukoc Biol. 2006 Jun;79(6):1131-9. doi: 10.1189/jlb.0106027. Epub 2006 Apr 14.
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.
肿瘤相关嗜酸性粒细胞增多现象已在多种人类癌症及多种动物肿瘤模型中被观察到；然而，围绕这种嗜酸性粒细胞增多的细节在很大程度上仍不明确且多为轶事性描述。我们使用B16 - F10黑色素瘤细胞注射模型来证明，肿瘤的嗜酸性粒细胞浸润从最早可触及阶段就已发生，且仅在坏死区域和包膜区域有显著聚集。此外，嗜酸性粒细胞主要碱性蛋白的弥漫性细胞外基质染色仅局限于肿瘤的坏死区域，这表明嗜酸性粒细胞脱颗粒仅限于该区域。抗体介导的CD4 + T细胞耗竭和嗜酸性粒细胞的过继转移分别表明，嗜酸性粒细胞的聚集与2型辅助性T细胞依赖性免疫反应无关，且招募是一个动态的、持续的过程，在肿瘤生长的全过程中都在发生。体外迁移研究已确定，应激/濒死黑色素瘤细胞似乎释放了一种新的趋化因子，这表明肿瘤中嗜酸性粒细胞的聚集部分是通过一种依赖于坏死区域释放的信号的独特机制发生的。总体而言，这些研究表明，嗜酸性粒细胞对肿瘤的浸润是一种早期且持续的反应，且在空间上受到限制。更重要的是，这些数据还表明，引发这种宿主反应的机制独立于免疫监视而发生，这表明嗜酸性粒细胞是肿瘤发生部位早期炎症反应的一部分。
