Tumor-associated galectin-3 modulates the function of tumor-reactive T cells.
Tumor-associated galectin-3 modulates the function of tumor-reactive T cells.
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DOI：
10.1158/0008-5472.can-08-1245
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发表时间：
2008-09-01
期刊：
影响因子：
11.2
通讯作者：
Wang RF
中科院分区：
文献类型：
--
作者：
Peng W;Wang HY;Miyahara Y;Peng G;Wang RF
T细胞在肿瘤免疫监视和肿瘤破坏中发挥着重要作用。然而，肿瘤细胞通过抗原刺激和免疫调节细胞因子调节免疫细胞，从而改变免疫应答。更好地了解肿瘤细胞和T细胞之间的相互作用可能为增强抗肿瘤免疫提供新的策略。通过使用结直肠肿瘤反应性T细胞的抗原筛选方法，我们鉴定了由KIAA0040编码的hla - dr11限制性T细胞表位以及由肿瘤细胞表达的mhc -不受限制的人半乳糖凝集素-3 （Gal-3）。虽然KIAA0040的生物学功能仍有待确定，但我们发现半乳糖凝集素-3可作为直接T细胞激活和功能的免疫调节剂。半凝集素-3诱导T细胞活化导致T细胞凋亡。我们发现半乳糖凝集素-3的高水平表达促进了肿瘤的体外和体内生长。通过小鼠肿瘤模型，我们证明了在接受肿瘤反应性CD8+ T细胞的小鼠中，高剂量半乳糖凝集素-3的递送抑制肿瘤反应性T细胞并促进肿瘤生长。这些发现提示半乳糖凝集素-3可能作为一种免疫调节剂抑制T细胞免疫应答，促进肿瘤生长，从而为肿瘤免疫耐受提供了新的机制。
T cells play an important role in cancer immunosurveillance and tumor destruction. However, tumor cells alter immune responses by modulating immune cells through antigen stimulation and immunoregulatory cytokines. A better understanding of the interplay between tumor cells and T cells might provide new strategies to enhance anti-tumor immunity. Through an antigen-screening approach using colorectal tumor-reactive T cells, we identified a HLA-DR11-restricted T-cell epitope encoded by KIAA0040 as well as MHC-unrestricted human galectin-3 (Gal-3) expressed by tumor cells. Although the biological function of KIAA0040 remains to be determined, we found that galectin-3 functioned as an immune regulator for direct T cell activation and function. T cell activation induced by galectin-3 resulted in T cell apoptosis. We showed that a high level of expression of galectin-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we demonstrated that delivery of high doses of galectin-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8+ T cells. These findings suggest that galectin-3 may function as an immune regulator to inhibit T cell immune responses and promote tumor growth, thus providing a new mechanism for tumor immune tolerance.