Annals of Oncology 12:S125-S130, 2001
© 2001 European Society for Medical Oncology
Reviews |
Neuroendocrine aspects of immunolymphoproliferative diseases
1 Department of Internal Medicine Rotterdam, the Netherlands
2 Di.S.E.M. Department of Endocrinological and Metabolic Sciences, University of Genova Naples, Italy
3 Department of Molecular & Clinical Endocrinology and Oncology, ‘Federico II’ University Naples, Italy
4 Department of of Immunology, Erasmus University Rotterdam, the Netherlands
Correspondence to: D. Ferone, MD, PhD Di.S.E.M., Department of Endocrinological and Metabolic Sciences University of Genova Viale Benedetto XV, 6 16132 Genova Italy E-mail: dferone{at}hotmail.com
Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation and mitogenesis, and immune cells may produce neuropeptides as well. Neuropetide Y is synthesized in B-cell leukaemia lymphoblasts, while substance P immunoreactivity has been detected in neoplastic haematological samples of different types of leukaemias. The presence of receptors for neuropeptides on different animal and human lymphoid cell lines, as well as in several types of animal and human lymphoproliferative diseases has been demonstrated. Species variability in receptor distribution has been shown as well. Receptor expression in immune cells may be regulated by changes in microenvironmental conditions; it may also be related to the activation and/or proliferation state of cells. Vasoactive intestinal peptides receptors have been detected in myeloma cells, while somatos tatin receptors have been first detected in vitro on resting lymphocytes and cells of the monocyte/macrophage lineage, and later on human activated lymphocytes and on lymphoblastic leukaemia cells. Somatostatin receptors have been found in biopsies from patients with malignant lymphomas. Tumor localization in non-Hodgkin lymphomas and Hodgkin's disease can be visualized by in vivo somatostatin receptor scintigraphy, contributing to establish the diagnosis and the stage of the disease. Recently, somatostatin receptors have been in vivo and in vitro detected in human thymic tumors. Although treatment of lymphoproliferative diseases with somatostatin analogs is a little explored field, partial remission was found in patients with low-grade non-Hodgkin lymphoma and cutaneous T-cell lymphoma, and a successful treatment with octreotide has been reported in patients with thymoma. Specific somatostatin receptors present in progenitors of immune cells are not expressed in the mature phenotype, while they can be detected in transformed cell lines. The possibility that this phenomenon is caused by oncogene expression can not be ruled out. Moreover, preliminary data showed a developmental expression of somatostatin receptors in lymphoid cells, suggesting a potential role for neuropeptide receptors as differentiation markers. Although controlled studies are warranted to investigate the efficacy of the currently available analogs, somatostatinergic compounds may be of interest in the treatment of lymphoproliferative malignancies. A promising approach in refractory patients with somatostatin receptor positive malignant lymphomas may be radionuclide-targeted and cytotoxic analog therapy. These concepts increase the possibility of a wider antitumor treatment with ligands for neuroepeptide receptors than in established ‘classic’ neuroendocrine tumors.
immune system, lymphoma, leukaemia, neuro endocrine differentiation, octreotide, somatostatin receptors