Thymic hormones in cancer diagnostics and treatment.
The thymus is an endocrine organ. A unified, physiological concept of humoral regulation of the immune response emerged in the last three decades. The thymus is the primary major site of production of immunocompetent T-lymphocytes from their haematopoietic stem cells. The thymus provides a superior humoral microenvironment for the development of immunocompetent T-lymphocytes. Although yolk sac derived pre-T stem cells enter the thymus using a homing receptor, the immigration process requires also secretion of a peptide, called thymotaxin by the cells of the reticulo-epithelial (RE) network. This complex process requires direct cell to cell, receptor based interactions, as well as in situ paracrine information via the numerous cytokines and thymic hormones produced by the RE cells of thymic microenvironment. Thymic hormones induce in situ T-lymphocyte marker differentiation, expression and functions. These polypeptide hormones have also been shown by means of immunocytochemistry to localise in the RE cells of the thymic cellular microenvironment. Based on the complexity of the intrathymic maturation sequence of T-lymphocytes and the increasing numbers of T-lymphocyte subpopulations that are being identified, it would be surprising if a single thymic humoral factor could control all of the molecular steps and cell populations involved. Rather, it would appear that the control of intrathymic T-lymphocyte maturation and functional maturation involves a complex number of thymic-specific factors and other molecules that rigidly control the intermediary steps in the differentiation process. Thymosin fraction 5 (TF5) and its component polypeptides influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production and expression of certain surface maturation/differentiation markers. Recently, thymic hormones, mostly thymosins have been employed not only in neoplasms' early detection but also in clinical trials to strengthen the effects of immunomodulators in immunodeficiencies, autoimmune diseases and neoplastic malignancies. Combined chemoimmunotherapeutical antineoplastic treatment seems to be useful. Generally, haematopoietic toxicity of every chemotherapeutical clinical trial can be reduced significantly by the immunotherapy, compared to 50% in patients treated with chemotherapy alone.
Bodey
B
B
Childrens Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles, Los Angeles, CA, USA. Bodey18@aol.com
D000818:Animals; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis; D006728:Hormones / Q000096:biosynthesis* / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D009479:Neuropeptides / Q000378:metabolism; D013950:Thymus Gland / Q000737:chemistry* / Q000378:metabolism*
D016207:Cytokines; D006728:Hormones; D009479:Neuropeptides