| Immune escape in tumorous tissue and immune anitumor plays a key role in the tumor development, these mechanisms are very complicate, relating to the expression of special tumor antigens and the immune inhibitors secreted by the tumor cells and the immune adhesion of malignant cells and so on. Cellular immune, especially T toxic lymphocyte plays an important role in antitumor immune. T lymphocytes are actived through T cell receptor (TCR) combinding with MHC on the membrane of antigen presenting cells, immune costimulator B7 working as the second stimulator presents associating messages for TCR/CD3. Low or absent expression of B7 makes T cells anergy, so costimulator is an important message system in acting T lymphocytes. We examined the expression of MHC- II and costimulatory molecules on acute nonlymphocytic leukemia (ANLL) bone marrow cells containing more than 70% leukemia blasts from 27 patients in primary stage or relapse stage, and the phenotype and function of the dendritic cells formed from peripheral blood monocyte cells (PBMNCs) of patients with CML and K562 cells in vitro. The results showed that the expression of HLA-DR was high in all but which were culured with cytokins ANLL-M3 patients, the highestabout 90% in M2. The expression of costimulatory molecule CD80 (B7-1) was low about 5% in Ml and 1-3% in other groups, CD86 (B7-2) expressed highly from 11% to 48%. PBMNCs of CML and K562 cells which were incubated concurrently with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-a (TNF-a) for 14 days were induced into leukemic dendritic cells (L-DC) which were examed their phenotype by FACS and their antigen present functions by cytotoxity test. L-DC showed typical dendritic morphology, expressed high levels of CD la. Analysis of chromosome showed the presence of t(9;22) in these cells. T cells stimulated with L-DC showed strong cytotoxic responses against leukemic cells. These results indicated that CD80 expression is low or absent in costimulatory molecules of ANLL blast cell, and that DC driven in vitro from cells of CML and K562 has a potent T cell stimulatory function and can inhibit the proliferation of leukemia cells, and these may be a newpathway for the immunotherapy of leukemia.In clinical immunotherapy, we treated an 82-year-old male with ANLL (M7) developed from MDS using interleukin-2 (IL-2). On diagnosis, the bone marrow showed 90.8% blast cells. After using EL-2 (1x106 U/d), Wast cells lowed to less 20% by day 120 This PR has lasted for 17+ months, at this time in the peripheral blood the white blood cells hemoglobin and platelets were normal. In hematopoietic stem cells transplantation, we transplanted autologous stem cell mixed with HLA-haploidentical allogeneic marrow. To decrease relapse after this mixed transplantation, we designed the immunotherapy by IL-2 and GM-CSF or IL-2 and DLL The first therapy was used in 5 patients and the second in 2 cases. All patients did not show significant side-effect, and could have a low relapse rate. Especially in 2 cases treated with IL-2 and DLI, they had no side effect during this immunotherapy besides temporary fever in one Chimerism and acute or chronic GVHD were not found. Two patients have lived without leukemia for 24 and 18 months respectively. From these clinical trials, we conclude that new treatmentoptions such as immunotherapy including IL-2 alone and IL-2 and GM-CSF or DLI for leukemia may be of clinical use in the treatment of malignant hemopoietic diseases. Further studies are warranted to evaluate the role of these immunotherapies in the traetment of leukemia.
|
PDF Full Text Request