Eosinophil ETosis and Cancer: Ultrastructural Evidence and Oncological Implications

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.