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      Immunotherapy of prolactinoma with a T helper 1 activator adjuvant and autoantigens: a case report.

      Neuroimmunomodulation
      Adjuvants, Immunologic, therapeutic use, Adult, Autoantigens, immunology, Bromocriptine, Female, Hormone Antagonists, Humans, Immunotherapy, methods, Lymphocyte Activation, Magnetic Resonance Imaging, Neoplasm Recurrence, Local, therapy, Pituitary Neoplasms, Prolactin, blood, Prolactinoma, Th1 Cells

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          Abstract

          To date, efforts to reliably manipulate the immune system to promote tumor regression in the brain have been disappointing. We report a unique experience of successful immunotherapy to treat a pituitary macroprolactinoma. A 31-year-old woman with an established history of pituitary macroprolactinoma who had undergone tumor resection followed by radiation was admitted to our clinic. The diagnosis had been made due to the patient's symptoms, a serum prolactin (PRL) level of 29,600 mIU/l, a brain MRI revealing a 23 x 19 x 18 mm pituitary mass and a positive PRL immunohistochemistry of the mass. Six months following surgery, she reexperienced headache, excessive sweating and a serum PRL concentration of 2,960 mIU/l despite receiving 30 mg/day bromocriptine. Brain MRI revealed a pituitary mass (3 x 6 x 8 mm) compatible with a pituitary adenoma. Twenty micrograms per milliliter of G2 (as a T helper 1 activator adjuvant) was inoculated intradermally once per week for 24 consecutive weeks (each injection contained 10 mug of G2). The autoantigens were inoculated at the same time with G2. After immunotherapy, serum PRL concentration decreased to 82 mIU/l, the patient's symptoms disappeared, skin thickness increased to normal and bromocriptine dosage was tapered to 20 mg per week. A follow-up brain MRI revealed almost complete disappearance of the tumor. The patient does not complain of any problems at 1-year follow-up. Activation of both nonspecific (natural killer cells) and specific (cytotoxic T lymphocytes) immunity in relation to the T helper 1 cytokine network is a promising strategy for the treatment of tumors of the central nervous system in humans, especially pituitary macroprolactinomas.

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          Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo.

          Cytotoxic T lymphocytes and natural killer cells are essential effectors of anti-tumor immune responses in vivo. Dendritic cells (DC) 'prime' tumor antigen-specific cytotoxic T lymphocytes; thus, we investigated whether DC might also trigger the innate, NK cell-mediated anti-tumor immunity. In mice with MHC class I-negative tumors, adoptively transferred- or Flt3 ligand-expanded DC promoted NK cell-dependent anti-tumor effects. In vitro studies demonstrated a cell-to-cell contact between DC and resting NK cells that resulted in a substantial increase in both NK cell cytolytic activity and IFN-gamma production. Thus, DC are involved in the interaction between innate and adaptive immune responses.
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            Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells

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              Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells

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