Tumor vaccination that enhances antitumor T-cell responses does not inhibit the growth of established tumors even in combination with interleukin-12 treatment: The importance of inducing intratumoral T-cell migration

P. Gao, Y. Uekusa, C. Nakajima, M. Iwasaki, M. Nakahira, Y. F. Yang, S. Ono, T. Tsujimura, H. Fujiwara, T. Hamaoka

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-12 (IL-12) treatment is effective in the CSA1M but not in the Meth A and CSA1M-variant tumor models. The authors investigated the cause by which IL-12 treatment fails to induce tumor regression in these two tumor models. T cells from CSA1M-bearing mice have high levels of IL-12 responsiveness, whereas cells from Meth A-bearing mice display marginal levels of responsiveness. Because IL-12 responsiveness in T cells is induced after T-cell receptor stimulation, the lack of IL-12 responsiveness suggests that T cells in Meth A-bearing mice are not sensitized to Meth A tumor antigen. Immunization of normal mice with attenuated Meth A tumor cells resulted in a protective immunity, as shown by the rejection of challenged viable Meth A cells. Such an immunization, when performed in Meth A-bearing mice, induced potent IL-12 responsiveness in T cells. Nevertheless, IL-12 treatment in these mice did not inhibit tumor growth. In another IL-12-incurable (CSA1M-variant) model, IL-12 responsiveness was observed before tumor cell immunization. However, IL-12 treatment was ineffective regardless of whether tumor cell immunization was performed. In these two models, the failure of IL-12 treatment to induce tumor regression was associated with the lack of T-cell migration to tumor sites. These results indicate that the sensitization of T cells to tumor antigens and generation of IL-12 responsiveness are insufficient to induce tumor regression when these sensitized T cells are not allowed to migrate to tumor sites.

Original languageEnglish (US)
Pages (from-to)643-653
Number of pages11
JournalJournal of Immunotherapy
Volume23
Issue number6
DOIs
StatePublished - 2000

Keywords

  • Interleukin-12
  • T-cell migration
  • Tumor vaccination

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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