TY - JOUR
T1 - Tumor vaccination that enhances antitumor T-cell responses does not inhibit the growth of established tumors even in combination with interleukin-12 treatment
T2 - The importance of inducing intratumoral T-cell migration
AU - Gao, P.
AU - Uekusa, Y.
AU - Nakajima, C.
AU - Iwasaki, M.
AU - Nakahira, M.
AU - Yang, Y. F.
AU - Ono, S.
AU - Tsujimura, T.
AU - Fujiwara, H.
AU - Hamaoka, T.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Interleukin-12
KW - T-cell migration
KW - Tumor vaccination
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U2 - 10.1097/00002371-200011000-00005
DO - 10.1097/00002371-200011000-00005
M3 - Article
C2 - 11186152
AN - SCOPUS:0033708117
SN - 1053-8550
VL - 23
SP - 643
EP - 653
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 6
ER -