INHIBITORY EFFECT OF METASTASIS BY COMBINED ADMINISTRATION WITH INTERLEUKIN-2 AND SIZOFIRAN, A SINGLE GLUCAN - IMMUNOHISTOCHEMICAL STUDY

Innovations in methods of combined administration with other BRM or ch emotherapeutic drugs have been discussed. We have reported [I] that co mbined administration with recombinant interleukin-2 (rIL-2) and sizof iran (SPG) is effective in prolonging survival time of C57BL/6 mice in traperitoneally inoculated with EL-4 lymphoma. The immunomechanisms of the combined administration were clarified investigating the intraper itoneal cell population in the primary tumor site, especially the tumo r infiltrating lymphocyte (TIL) quantitatively. In the present study, to clarify the antitumor effects of combined administration with rIL-2 and SPG on the metastatic sites, the immnunomechanisms of the suppres sive effects of combined administration on the metastasis were studied in EL-4 lymphoma cells intraperitoneally transplanted to mice. Inasmu ch as EL-4 lymphoma shows rapid hepatosplenic metastasis, we studied t he metastatic foci in the liver and the spleen semiquantitatively inve stigating the histopathological and immunohistochemical findings of th e metastatic foci, especially the TIL. The metastatic foci were staine d by hematoxylin-eosin (HE) and monoclonal antibodies (L3T4, Lyt2, asi alo GM1, Mac-1, and Ia). The combined administration resulted in: 1) f ewer infiltrating tumor cells, 2) more lymphocytic infiltration, and 3 ) more antitumor effector cells (cytotoxic T cells: Lyt2 and natural k iller cells: asialo GM1), macrophages (Mac-1), helper T cells (L3T4), and cells with MHC-class-II antigen (Ia) than did administration of rI L-2 alone or SPG alone, or no administration of these two at all. Comb ined administration with rIL-2 and SPG appears to activate antitumor-i mmune response at the metastatic site more effectively than when eithe r agent is administered alone.