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
| Autor: | Takahiro Tsujimura, Masakiyo Nakahira, Yi-Fu Yang, Masayuki Iwasaki, Chigusa Nakajima, Ping Gao, Shiro Ono, Toshiyuki Hamaoka, Hiromi Fujiwara, Yasuhiro Uekusa |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Cancer Research Fibrosarcoma medicine.medical_treatment T cell Immunology Cancer Vaccines Mice chemistry.chemical_compound Lymphocytes Tumor-Infiltrating Immune system Antigen Antigens Neoplasm Histocompatibility Antigens Tumor Cells Cultured Animals Immunologic Factors Immunology and Allergy Medicine Pharmacology Mice Inbred BALB C business.industry Tumor-infiltrating lymphocytes Immunotherapy Meth Combined Modality Therapy Interleukin-12 Tumor antigen medicine.anatomical_structure chemistry Interleukin 12 business Cell Division T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Immunotherapy. 23:643-653 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/00002371-200011000-00005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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