IWASAKI Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title 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.
Journal Formal name:Journal of immunotherapy (Hagerstown, Md. : 1997)
Abbreviation:J Immunother
ISSN code:15249557/15249557
Domestic / ForeginForegin
Volume, Issue, Page 23(6),pp.643-53
Author and coauthor Gao P, Uekusa Y, Nakajima C, Iwasaki M, Nakahira M, Yang Y F, Ono S, Tsujimura T, Fujiwara H, Hamaoka T
Publication date 2000/11
Summary 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.
DOI 10.1097/00002371-200011000-00005
PMID 11186152