Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers.
嗜酸性粒细胞是先天性免疫细胞，在正常损伤修复、寄生虫感染、过敏反应及癌症过程中，会因细胞增殖与坏死而浸润组织。其在癌症中的作用存在争议，尤其涉及肿瘤相关组织嗜酸性粒细胞增多（TATE）以及近期定义的细胞外诱捕网死亡机制（ETosis）——这是一种区别于细胞凋亡与坏死的特殊嗜酸性粒细胞死亡方式。本文综述了关于TATE预后意义的文献，重点关注嗜酸性粒细胞ETosis现象，以及透射电子显微镜（TEM）在其检测与形态学表征中的关键作用。TATE的预后作用存在矛盾：在某些肿瘤中它是良好的预后标志物，而在另一些肿瘤中则提示不良预后。然而最新研究表明，TATE与非病毒性肿瘤的良好预后相关，但在病毒相关肿瘤（如人类T淋巴细胞病毒1型相关淋巴瘤和人乳头瘤病毒阳性癌）中可能与不良预后相关。我们的超微结构研究揭示了胃癌中嗜酸性粒细胞ETosis的典型阶段，其特征包括染色质解聚、质膜破裂、颗粒释放及细胞外诱捕网形成。我们观察到发生ETosis或复合胞吐的嗜酸性粒细胞与肿瘤细胞之间存在类突触相互作用，后者呈现不同程度的细胞损伤，最终导致胶体渗透性肿瘤细胞死亡。TEM为理解嗜酸性粒细胞介导的细胞毒性提供了重要视角，这种机制在非病毒性肿瘤中作为潜在免疫效应机制值得深入研究。结合肿瘤的病毒状态进行TATE评估，可能有助于确认其预后意义，进而为特定癌症的治疗策略提供参考。
Eosinophil ETosis and Cancer: Ultrastructural Evidence and Oncological Implications
肿瘤(癌症)患者之家