Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study

J Neurosurg. 2005 Jan:102 Suppl:180-4. doi: 10.3171/jns.2005.102.s_supplement.0180.


Object: The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS).

Methods: Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration.

Conclusions: Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology*
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / surgery
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Craniotomy
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / immunology*
  • Lymphoid Tissue / immunology
  • Neoplasms, Second Primary
  • Radiosurgery / instrumentation*
  • Tumor Burden / radiation effects


  • Antigens, CD