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
somatostatin 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 cannot 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.