https://scholars.lib.ntu.edu.tw/handle/123456789/290279
標題: | Tumor-induced immunosuppression: A barrier to immunotherapy of large tumors by cytokine-secreting tumor vaccine | 作者: | Hsieh, C.-L. DING-SHINN CHEN Hwang, L.-H. |
公開日期: | 2000 | 卷: | 11 | 期: | 5 | 起(迄)頁: | 681-692 | 來源出版物: | Human Gene Therapy | 摘要: | An active immunotherapy strategy with cytokine-assisted tumor vaccine, although often effective for small tumor burdens, is much less so for large tumor burdens. This study examines how large tumors might suppress the T cell functions and escape from the immune responses elicited by a granulocyte- macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine. According to our results, the T cells isolated from the tumor-bearing mice treated late with the vaccine failed to confer protective activity on naive mice against a wild-type tumor challenge, unlike those isolated from the early-treated group. Nevertheless, the antitumor activity of the inactive T cells could be restored on in vitro stimulation. Expression of transforming growth factor β (TGF-β) and interleukin 10 (IL-10), the potent immunosuppressive factors, was detected in the parental tumor cell line RL♂ 1 (a murine T leukemia cell line), as well as in the tumor region, the levels of which correlated with tumor progression. An in vitro assay of T cell functions revealed that the TGF-β in the conditioned medium of RL♂ 1 cells mainly affected the activation, whereas the IL-10 affected the activation to a lesser extent, but significantly affected the cytolytic activity, of tumor- specific T cells. The immunosuppressive activity of IL-10 was also signified by the findings that administration of the conditioned medium of RL♂ 1 cultured in a serum-free medium, in which the TGF-β activity was then lost while the IL-10 activity still remained, or of recombinant IL-10 to the early-treated group of mice abrogated the known efficacy of tumor vaccine on the small tumors. These data suggested that the efficacy of cytokine- secreting tumor vaccine was blocked by the immunosuppressive factors secreted from the large tumors. The results have important implications for the clinical design of immunotherapeutic strategies for advanced cancer patients. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034689206&doi=10.1089%2f10430340050015581&partnerID=40&md5=beaa3143d462af3257a94730ef9d429f http://scholars.lib.ntu.edu.tw/handle/123456789/290279 |
DOI: | 10.1089/10430340050015581 | SDG/關鍵字: | granulocyte macrophage colony stimulating factor; interleukin 10; transforming growth factor beta; tumor vaccine; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer immunotherapy; controlled study; cytotoxic T lymphocyte; immune deficiency; male; mouse; murine leukemia; nonhuman; tumor associated leukocyte; tumor escape; Animals; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Division; Culture Media, Conditioned; Cytokines; Immunosuppression; Immunotherapy; Interleukin-10; Leukemia, Experimental; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Recombinant Proteins; T-Lymphocytes; Transforming Growth Factor beta; Animalia; Murinae |
顯示於: | 醫學系 |
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