Cyclophosphamide given after active specific immunization augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells

Autor: Seiji Yamasaki, Li Li, You Ichinose, Norimichi Kan, Takashi Okino, Tomoharu Sugie, Shunji Kanaoka, Masayuki Imamura
Rok vydání: 1998
Předmět:
Zdroj: Journal of Surgical Oncology. 67:221-227
ISSN: 1096-9098
0022-4790
Popis: Background and Objectives: In order to evaluate the regulatory effect of cyclophosphamide (CPA) on active specific immunization (ASI)-induced antitumor immunity, we examined the timing of CPA (100 mg/kg) with ASI, and focused on whether CPA given after ASI augments antitumor immunity by modulation of Th1 commitment of CD4 + T cells. Methods: We examined the effect of CPA combined with ASI using sonicated tumor supernatant (SS) and recombinant interleukin-1 β (rIL-1 β). Results: Survival of i.p. tumor inoculated mice after ASI (days -12, -9, and -6) followed by 100 mg/kg CPA (day -3) (ASI-CPA) was significantly prolonged compared with that of mice treated with ASI alone, whereas CPA (day -15) treatment before ASI (CPA-ASI) completely abrogated the survival prolongation by ASI alone. In early stage (day 0) after ASI-CPA treatment, the CD4 + T cells were determined to play an important role in the protective immunity for the following reasons: 1) the CD4 + /CD8 + ratio of spleen cells from immunized mice was higher than that of the control or CPA alone treated group; and 2) the tumor neutralizing activity of fresh spleen cells was abrogated by CD4 + T-cell depletion in vitro. CD4 + T cells of mice treated with ASI-CPA produced more interferon (IFN)-γ and IL-2 and less IL-4 than those of the ASI alone group. Conclusions: These results suggest that the protective immunity induced by ASI was augmented through the modification of the Thl and Th2 balance by CPA injection after ASI.
Databáze: OpenAIRE
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