Review of thymic hormones in cancer diagnosis and treatment

The thymus is an endocrine organ, A unified, physiological concept of humor al regulations of the immune response has emerged in the last three decades . The thymus is the major site of production of immunocompetent T lymphocyt es from their hematopoietic stem cells. This complex process required direc t cell to cell, receptor based interactions, as well as in situ paracrine i nformation via the numerous cytokines and thymic hormones produced by the c ells of thymic microenvironment. Thymic hormones induce in situ T-cell mark er differentiation, expression and functions. These polypeptide hormones ha ve also been shown by means of immunocytochemistry to localize in the retic ulo-epithelial (RE) cells of the thymic cellular microenvironment. Due to t he great complexity of the intrathymic maturation sequence of T lymphocytes and the diverse immunophenotypically unique subpopulations of T lymphocyte s, it is quite unlikely that a single thymic humoral factor could control a ll of the molecular steps and cell populations involved. It is much more li kely that an extremely rich and diverse, but genetically determined, milieu is present within the thymus, and that thus the control of intrathymic T l ymphocyte maturation and the functional maturation of T cells involves the orchestral interaction of various thymic-specific factors and other molecul es during the differentiation process. Thymosin fraction 5 and its constitu ent peptides influence several properties of lymphocytes including cyclic n ucleotide levels, migration inhibitory factor production, T-dependent antib ody production, as well as the expression of various cell surface maturatio n/differentiation markers. Recently, derivatives of thymic hormones, mostly of thymosins, have been detected as products of neoplastically transformed cells and employed in the early diagnosis of neoplasms. In clinical trials , thymic hormones strengthen the effects of immunomodulators in immunodefic iencies, autoimmune diseases, and neoplastic malignancies. Combined chemoim munotherapeutical anti-cancer treatment seems to be more efficacious than c hemotherapy alone, and the significant hematopoietic toxicity associated wi th most chemotherapeutical clinical trials can be reduced significantly by the addition of immunotherapy. (C) 2000 International Society for Immunopha rmacology. Published by Elsevier Science Ltd. All rights reserved.