Toll-like receptors on tumor cells facilitate evasion of immune surveillance (Publication with Expression of Concern. See vol. 79, pg. 4305, 2019)
Toll-like receptors on tumor cells facilitate evasion of immune surveillance (Publication with Expression of Concern. See vol. 79, pg. 4305, 2019)
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DOI：
10.1158/0008-5472.can-05-0784
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Xiong, HB
中科院分区：
文献类型：
--
作者：
Huang, B;Zhao, J;Xiong, HB
触发肿瘤细胞逃避免疫监视的信号通路尚不完全清楚。toll样受体（TLRs）激活先天和适应性免疫反应，被认为仅限于免疫细胞。我们在这里表明，TLR，包括TLR4，在多种组织的肿瘤细胞上表达，这表明TLR激活可能是肿瘤细胞免疫逃避的一个重要事件。通过脂多糖激活肿瘤细胞中的TLR4信号，诱导多种可溶性因子和蛋白的合成，包括白细胞介素-6、诱导型一氧化氮合酶、白细胞介素-12、B7-H1和B7-H2，导致肿瘤细胞抵抗CTL攻击。此外，脂多糖刺激的肿瘤细胞上清液抑制T细胞增殖和自然杀伤细胞活性。通过TLR4短干扰RNA或细胞渗透性TLR4抑制肽阻断TLR4通路，在体外可逆转肿瘤介导的T细胞增殖和自然杀伤细胞活性抑制，在体内可延缓肿瘤生长，从而延长荷瘤小鼠的生存期。这些发现表明，TLR信号导致级联导致肿瘤逃避免疫监视。tlr在肿瘤生物学中的这些新功能为癌症治疗提供了一类新的治疗靶点。
The signal pathways that trigger tumor cell escape from immune surveillance are incompletely understood. Toll-like receptors (TLRs), which activate innate and adaptive immune responses, are thought to he restricted to immune cells. We show here that TLRs, including TLR4, are expressed on tumor cells from a wide variety of tissues, suggesting that TLR activation may be an important event in tumor cell immune evasion. Activation of TLR4 signaling in tumor cells by lipopolysaccharide induces the synthesis of various soluble factors and proteins including interleukin-6, inducible nitric oxide synthase, interleukin-12, B7-H1, and B7-H2, and results in resistance of tumor cells to CTL attack. In addition, lipopolysaccharide-stimulated tumor cell supernatants inhibit both T cell proliferation and natural killer cell activity. Blockade of the TLR4 pathway by either TLR4 short interfering RNA or a cell-permeable TLR4 inhibitory peptide reverses tumor-mediated suppression of T cell proliferation and natural killer cell activity in vitro, and in vivo, delays tumor growth and thus prolongs the survival of tumor-bearing mice. These findings indicate that TLR signaling results in a cascade leading to tumor evasion from immune surveillance. These novel functions of TLRs in tumor biology suggest a new class of therapeutic targets for cancer therapy.