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TUMOUR IMMUNOLOGY

Chemokine-driven transmigration of regulatory T cells into the central nervous system of patients with B-cell non-Hodgkin lymphoma

 

We are investigating whether regulatory T cells (Treg) counteract antitumor immunity in patients with neoplastic meningitis and whether Treg are enriched in the cerebrospinal fluid of these patients. Our results reinforce existing studies, suggesting an important role of Treg in the survival and growth of malignant cells. Intriguingly, Treg may counteract local antitumor immune responses even more efficiently than outside the central nervous system, where the movement of tumor-infiltrating conventional human T cells is less restricted by barrier structures. Proof of concept will provide a rationale for manipulating Treg to enhance immunotherapy for patients with lymphomatous or carcinomatous neoplastic meningitis.

Selected publications

  • Haas J, Schopp L, Storch-Hagenlocher B, Fritzsching B, Jacobi C, Milkova L, Fritz B, Schwarz A, Suri-Payer E, Hensel M, Wildemann B. Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis. Blood 2008;111:761-6.
  • Wildemann B, Haas J, Schopp L, Hensel M. Specific recruitment of regulatory T cells into the cerebrospinal fluid in neoplastic meningitis. Neurology 2008;68(s1):A291-2.

Molecular analysis of B-cell clonality in cerebrospinal fluid: diagnostic significance in meningeosis blastomatosa

Principal investigator: Brigitte Storch-Hagenlocher

Diagnosis of meningeosis blastomatosa (MB) is based on detection of malignant cells in the cerebrospinal fluid (CSF) by cytological evaluation. However, this is not always unequivocal and is often hampered by paucity of cells. We provide standardized molecular analysis of B cells in the CSF for diagnosis of MB. During normal B-cell maturation the immunoglobulin H gene (IgH) undergoes a complex rearrangement of the variable (VH), diversity (DH), and joining (JH) gene segments, resulting in clone-specific highly diverse VH-N-DH-N-JH junctions known as the third complementarity determining region (CDR3). In contrast, malignant B cells predominantly show identical recombination of the CDR3 region leading to monoclonal patterns in a PCR-based CDR3-specific DNA fragment analysis. We have optimized this technique and provide clone-specific CDR3 characterization at the single cell level for optimized diagnosis of MB in a routine setting.

Selected publications

  • Hug A, Storch-Hagenlocher B, Haas J, Vogt-Schaden ME, Goldschmidt H, Wildemann B. Single-cell PCR analysis of the immunoglobulin heavy-chain CDR3 region for the diagnosis of leptomeningeal involvement of B-cell malignancies using standard cerebrospinal fluid cytospins. J Neurol Sci 2004;219:83-8.
  • Hug A, Haas J, Storch-Hagenlocher B, Wildemann B. Leptomeningeale Tumorzell-Infiltration als Erstmanifestation eines Immunozytoms (M. Waldenström). Nervenarzt 2004;75:1012-5.
  • Wildemann B, Jansen O, Haas J, Vogt-Schaden ME, Storch-Hagenlocher B. Rapid distinction of acute demyelinating disorders and central nervous system lymphoma by molecular analysis of cerebrospinal fluid cells. J Neurol 2001;248:27-30.
  • Storch-Hagenlocher B, Haas J, Vogt-Schaden ME, Bentz M, Hoffmann LA, Biessmann A and Wildemann B. Molecular analysis of the CDR3 encoding region of the immunoglobulin heavy chain locus in cerebrospinal fluid cells as a diagnostic tool in lymphomatous meningitis. Ann Neurol 2000;47:211-7.