Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant XXXX .

@entity242 @entity2047 @entity5 @entity19 @entity1961 @entity3414
The systemic administration of high-dose recombinant @entity2047 mediated significant reductions of established 3-day pulmonary micrometastases from both weakly immunogenic and @entity242 . However, when treatment with @entity2047 was delayed for 10 days after the injection of @entity5 cells in an attempt to treat grossly visible pulmonary macrometastases, only those established from weakly @entity242 remained susceptible. Established 10-day pulmonary nodules from the @entity242 became refractory to @entity2047 therapy. We utilized selective depletion of lymphocyte subsets in vivo by the systemic administration of specific monoclonal antibodies to cells bearing either the @entity1961 or @entity3414 marker or a heteroantiserum to cells bearing the ASGM-1 glycosphingolipid to identify lymphocytes involved in @entity2047 -induced @entity5 regression. Cells with potent lymphokine-activated killer (LAK) activity against fresh @entity5 targets in vitro were identified in the lungs of @entity2047 -treated @entity19 . By flow cytometry analysis, the majority of these effector cells were Thy-1+, @entity1961 -, @entity3414 -, ASGM-1+. Depletion in vivo of ASGM-1+ cells before the onset of @entity2047 administration eliminated the successful therapy of 3-day pulmonary metastases from @entity242 , with concurrent elimination of LAK cell activity in the lungs. In @entity19 with 3-day pulmonary metastases from weakly @entity242 , both @entity3414 + cells and ASGM-1+ cells were involved in @entity2047 -mediated @entity5 regression, but @entity3414 + cells appeared to be the more potent mediator in the response. @entity3414 + cells were also involved in the elimination of grossly visible 10-day macrometastases from these weakly immunogenic @entity5 . Depletion of @entity1961 + cells had no effect on @entity5 regression. Thus, although LAK effectors derived from ASGM-1+ precursors can eliminate pulmonary micrometastases regardless of @entity5 immunogenicity, @entity3414 + cells are predominant effectors in the elimination of both pulmonary micro- and macrometastases from weakly @entity242 .
