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

Cancer Immunol Immunother. 1993;36(2):115-22. doi: 10.1007/BF01754411.

Abstract

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.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Surface / analysis
  • Cyclophosphamide / pharmacology*
  • Female
  • Immunity / drug effects
  • Immunotherapy, Adoptive
  • Male
  • Membrane Glycoproteins / analysis
  • Mice
  • Mice, Inbred CBA
  • Neoplasms, Experimental / immunology*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • Thy-1 Antigens

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • Membrane Glycoproteins
  • Thy-1 Antigens
  • Cyclophosphamide