Presence of D110 antigen expressing immunocompetent cells in glioblastoma associates with prolonged survival

Monoclonal antibody D110 has recently been described as a novel marker of hypoxic tissue damage, reacting with a so far unknown antigen with preferential expression in the central nervous system. The aim of the study was to investigate D110 immunoreactivity in glioblastoma, its association with the expression of hypoxia‐related proteins and its impact on patient outcome. A total of 114 consecutive adult patients who underwent first operation of primary glioblastoma were included in this study. We evaluated D110 immunoreactivity qualitatively and semi‐quantitatively and correlated it with expression of hypoxia inducible factor 1 alpha (HIF‐1α), expression of vascular endothelial growth factor (VEGF), and with patient survival using univariate and multivariate statistical analysis. We observed D110 immunolabelling in 85.1% of the cases. D110 immunoreactivity was detectable in infiltrating HLA‐DR and CD68 expressing cells, most likely microglial cells or haematogenous cells of monocyte/macrophage lineage. In the peripheral lymphoreticular system, immunohistochemistry disclosed selective D110 labelling of Langerhans cells and of dendritic cells of the thymic medulla. Univariate statistical analysis revealed significantly longer survival of patients whose glioblastomas contained D110 immunoreactive infiltrating cells. There was no association between presence of D110 immunoreactive cells and expression of HIF‐1α and VEGF. We conclude that D110 immunoreactivity in glioblastoma does not seem to be related to tissue hypoxia. D110 identifies immunocompetent cells, which positively influence survival of glioblastoma patients.

[1]  L. Palma,et al.  Lymphocytic infiltration in long-survival glioblastomas: Possible host's resistance , 2005, Acta Neurochirurgica.

[2]  K. Jellinger,et al.  A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions. , 2003, Brain : a journal of neurology.

[3]  Xiangpeng Yuan,et al.  Current and future strategies for the treatment of malignant brain tumors. , 2003, Pharmacology & therapeutics.

[4]  Markus Bredel,et al.  Vascular Patterns in Glioblastoma Influence Clinical Outcome and Associate with Variable Expression of Angiogenic Proteins: Evidence for Distinct Angiogenic Subtypes , 2003, Brain pathology.

[5]  M. Ollerenshaw,et al.  Expression of hypoxia‐inducible factor 1α in tumours of patients with glioblastoma , 2002, Neuropathology and applied neurobiology.

[6]  G. Reifenberger,et al.  The WHO Classification of Tumors of the Nervous System , 2002, Journal of neuropathology and experimental neurology.

[7]  M Molls,et al.  Perspectives in the treatment of malignant gliomas in adults. , 2001, Anticancer research.

[8]  K. Black,et al.  Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. , 2001, Cancer research.

[9]  M. Weller,et al.  Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives , 1999, Cellular and Molecular Life Sciences CMLS.

[10]  D. Avigan Dendritic cells: development, function and potential use for cancer immunotherapy. , 1999, Blood reviews.

[11]  F. Hochberg,et al.  Prognostic value of round cell (lymphocyte) infiltration in malignant gliomas. , 1985, Surgical neurology.

[12]  D. Böker,et al.  Mononuclear infiltrates in human intracranial tumors as a prognostic factor. Influence of preoperative steroid treatment. I. Glioblastoma. , 1984, Clinical neuropathology.

[13]  N. Di Lorenzo,et al.  Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas. Incidence, fate, and relevance to prognosis in 228 operated cases. , 1978, Journal of neurosurgery.

[14]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .