期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 3, 期 8, 页码 1061-1071出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S1567-5769(03)00060-2
关键词
cancer; cellular immunity; thymus; T lymphocytes; immunodeficiency; anergy immunosuppression; cytokines; thymomimetic agents; immunorestoration
Cellular immunodeficiency is associated with human cancer. Extensive reviews on cancer of the head and neck, lung, esophagus and breast convince the author that for these diseases the immunodeficiency is reasonably well established yet the mechanisms are poorly understood. Evidence indicates that other tumors are similarly associated with cellular immune deficiency. The advent of recombinant cytokines and of antitumor monoclonal antibodies has served to focus attention toward direct tumoricidal mechanisms. As tumor antigens relating to cellular and humoral immune mechanisms are being defined and vaccine strategies are increasingly being attempted, it is critical to confront issues of the mechanism of anergy and effective immunorestoration in order to maximize the potential of cellular immune response to address these tumor antigens. Intrinsic to this approach is the introduction of contrasuppressive therapy to alleviate the tumor-associated immune suppression. Encouraging attempts have been made with plasmapheresis, indomethacin, low-dose cyclophosphamide, anti CTLA-4, anti FAS ligand and, perhaps in the future, more judiciously applied chemotherapy. In contrast to the popular notion that thymic involution cannot be reversed in the adult, studies from the author's laboratory indicate that in aged hydrocortisone stressed mice, a natural Type 1-cytokine mixture (IRX-2) hastens the reversal of thymic involution and promotes T-cell responses to cytokines and mitogens. Recombinant IL-1 and IL-2 by themselves, and in combination, were inactive. Similar positive effects were observed with oral zinc, zinc-thymulin and thymosin alpha(1). The combination of a natural cytokine mixture (IRX-2) with thymosin alpha(1) had a very large effect and increased the absolute number of peripheral T lymphocytes as measured in the spleen. In studies of combination immunotherapy in lymphocytopenic squamous cell head and neck cancer patients using IRX-2 (18 patients) and IRX-2 plus thymosin alpha(1) (IRX-3) in IRX-2-refractory patients (7 patients), marked increases in CD(45)RA(+) naive T cells (>250/mm(3)) were observed. These are among the first insights into how to generate T lymphocyte replacement in the adult. These and many other experimental efforts point to ways to achieve more effective immunotherapy of human cancer in the future, particularly if tumor-induced immune deficiency can be effectively addressed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据