The influence of cyclophosphamide on antitumor immunity in mice bearing late-stage tumors

• Published in: Cancer Immunology Immunotherapy Vol. 36; no. 2; pp. 115 - 122
• Main Authors: CULO, F, KLAPAN, I, KOLAK, T
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.03.1993; Springer-Verlag
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - analysis; Antigens, Surface - analysis; Antineoplastic agents; Biological and medical sciences; Cyclophosphamide - pharmacology; Female; General aspects; Immunity - drug effects; Immunotherapy, Adoptive; Male; Medical sciences; Membrane Glycoproteins - analysis; Mice; Mice, Inbred CBA; Neoplasms, Experimental - immunology; Original; Pharmacology. Drug treatments; Spleen - drug effects; Spleen - immunology; T-Lymphocytes, Regulatory - drug effects; Thy-1 Antigens; Intraperitoneal administration; Immune response; Rodentia; Splenocyte; Malignant tumor; Cell subpopulation; Terminal stade; Vertebrata; Chemotherapy; Immunostimulant agent; Experimental disease; Phenotype; Mammalia; Treatment; Mouse; Animal; Suppressive cell; Mechanism of action
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF01754411

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.