行政院國家科學委員會專題研究計畫期中進度報告:犬傳染性花柳性腫瘤如何調控主要組織相容性複合體之表現以躲避宿主的免疫反應(2/3)
Date Issued
2003
Date
2003
Author(s)
朱瑞民
DOI
912313B002375
Abstract
IL-6 is a multifunctional cytokine that regulates cell growth, differentiation and
cell survival. Many tumor cells produce TGFβ1, which allows them to evade
cytotoxic T lymphocyte (CTL) mediated immune responses. IL-6 antagonizes TGFβ1
inhibition of CTL. However, whether IL-6 restores NK activity, which also is
suppressed by TGFβ1, is not known. We used canine transmissible venereal tumor
(CTVT), which produces TGFβ1, as a model to determine whether IL-6 restores NK
activity. During the progression (P) phase, CTVT cells stop expressing MHC
molecules, allowing them to evade the immune response mediated by CTL. During
the regression (R) phase, the number of surface MHC molecules increases
dramatically on about one third of tumor cells. Tumor cells that loss MHC expression
should be targeted by NK cells. In this study, we found that TGFβ1 secreted by CTVT
cells suppressed NK cytotoxicity, enabling tumor cells to escape host NK cell attack
during P phase. Interestingly, tumor infiltrating lymphocytes (TIL) isolated from
regressing CTVT secrete high concentrations of IL-6 and antagonize the anti-NK
activity of tumor cell TGFβ1. TIL also produce IL-6 during P phase, but the
concentration is too low to block the anti-NK activity of TGFβ1. There is probably a
threshold concentration of IL-6 needed to reverse TGFβ1-inhibited NK activity. In
addition, in the absence of TGFβ1, IL-6 derived from TIL does not promote the NK
killing activity of LAK cells. TIL-derived IL-6 restored the host NK killing activity
inhibited by tumor TGFβ1. This new mechanism, in which TIL manufacture high
concentrations of IL-6 to block tumor TGF-β1 anti-NK activity, has potential
applications in cancer immunotherapy and tumor prognosis.
SDGs
Publisher
臺北市：國立臺灣大學獸醫學系暨研究所
Type
report
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