The influence of cyclophosphamide on antitumor immunity in mice bearing late-stage tumors.
Spleen cells from mice bearing late-stage methylcholanthrene-induced tumor did not show any tumor activity when mixed with tumor cells in Winn's assay. Treatment of these mice with cyclophosphamide (CY) induced a tumor-inhibitory activity in spleen, occurring on day 7 after treatment, reaching its maximum on day 11 and disappearing by day 21. This antitumor activity could not be induced in control, tumor-free or T-deficient tumor-bearing mice. CY-induced tumor-inhibitory activity was immunologically specific, and mediated by Thy-1+, L3T4-, Ly-2+ cells. Contrary to spleen cells from untreated tumor-bearing mice, spleen cells from CY-treated tumor-bearing mice did not suppress the antitumor activity of immune spleen cells in Winn's assay. However, in contrast to immune spleen cells, CY-induced tumor-inhibitory cells did not manifest antitumor activity when transferred systemically (i.v.) into T-cell-deficient tumor-bearing mice. Even more, spleen cells from CY-pretreated mice, harvested 7-15 days after the drug administration, partially suppressed the antitumor activity of concomitantly transferred spleen cells from specifically immune mice. Nevertheless, CY-pretreated mice manifested concomitant immunity, i.e. these mice exhibited higher resistance to a second inoculum of the same tumor than did nontreated mice or even mice with excised primary tumor.
Culo
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F
Department of Physiology and Immunology, Zagreb University School of Medicine, Croatia.
Klapan
I
I
Kolak
T
T
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D007109:Immunity / Q000187:drug effects; D016219:Immunotherapy, Adoptive; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008808:Mice, Inbred CBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D018800:Thy-1 Antigens
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D003520:Cyclophosphamide