Effectiveness of immunotherapy in aged leukemic mice.
We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very effective in stimulating natural killer (NK) cells and in increasing the life span of young adult mice bearing a tumor of hemopoietic origin. The aim of the present study was to test the efficacy and universality, with respect to age, of this treatment in tumor-bearing mice. DBA/2 mice (10-16 months old) were injected with 5 x 10(6) erythroleukemia cells and remained either: (i) untreated (control); (ii) treated with indomethacin (5 micrograms/ml drinking water) for 9 days from tumor onset; (iii) treated with rIL-2 (24 x 10(3) U/injection) twice a day for the last 4 days of the 9-day tumor-bearing period, or (iv) treated with both indomethacin and rIL-2 concomitantly. Some mice from each group (above) were killed after 9 days of tumor growth, while the others were allowed to survive. Spleen and bone marrow cells were collected from the mice of each group and NK (ASGM-1+) cells were quantitated using an immunoperoxidase technique combined with light microscopy. NK cell-mediated activity was assessed using a standard chromium release assay. The results show that although NK cell numbers increase in the presence of the growing tumor, neither indomethacin alone, rIL-2 alone, nor the combination could further increase the numbers of these cells. Furthermore, indomethacin and/or rIL-2 could not induce NK cell-mediated activity in such mice. Moreover, tumor-bearing aged mice treated as above did not have a significantly longer life span than untreated (control) tumor-bearing mice. The present results indicate an age-dependent resistance to a form of immunotherapy already proven very effective in young adult mice. Furthermore, the results of this and our previous studies suggest that immunotherapy, which may be highly effective in one age group, should not be presumed effective throughout life.
Dussault
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Department of Anatomy and Cell Biology, McGill University, Montreal, Que., Canada.
Miller
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D000375:Aging / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D003131:Combined Modality Therapy; D007167:Immunotherapy; D007213:Indomethacin / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D007376:Interleukin-2; D011994:Recombinant Proteins; D007213:Indomethacin