Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangdong Province 510515, People's Republic of China.
Carcinogenesis. 2011 Mar;32(3):296-304. doi: 10.1093/carcin/bgq265. Epub 2010 Dec 13.
CC chemokine ligand 21 (CCL21) is a known attractant for CCR7-positive (CCR7+) cells, but its additional role in the immunogenicity of CCR7+ cells remains poorly understood. This study explored the effects of CCL21-CCR7 ligation on cancer immunogenicity and related antitumor immune response, in the presence and absence of mitomycin C (MMC) treatment. CCL21-CCR7 binding upregulated human leukocyte antigen class I-restricted tumor antigen presentation with increased expression of human leukocyte antigen class I and transporter associated with antigen processing-1. In addition, CCL21 restrained the tumor-derived immunosuppressive factors FasL and transforming growth factor-β. Consequently, CCL21 facilitated cancer-educated lymphocytes reaction in vitro. In the tumor-bearing mouse, CCL21 inhibited tumor growth and prolonged mouse survival via lymphocytes, especially in CCR7+ cancer cells. Furthermore, Toll-like receptor 2 activation of lymphocytes assisted the tumor-suppression functions of CCL21, in vitro and in vivo. This study implies that CCL21 improved the immunogenicity of the CCR7+ breast cancer cell line even with MMC treatment and triggered antitumor response by lymphocytes. These findings provide a new insight into the research and application of CCL21-associated antitumor response.
CC 趋化因子配体 21（CCL21）是 CCR7 阳性（CCR7+）细胞的已知趋化因子，但它在 CCR7+细胞免疫原性中的其他作用仍知之甚少。本研究探讨了 CCL21-CCR7 结合在存在和不存在丝裂霉素 C（MMC）治疗的情况下对癌症免疫原性和相关抗肿瘤免疫反应的影响。CCL21-CCR7 结合上调了人类白细胞抗原 I 类限制的肿瘤抗原呈递，增加了人类白细胞抗原 I 和抗原加工转运体-1 的表达。此外，CCL21 抑制了肿瘤来源的免疫抑制因子 FasL 和转化生长因子-β。因此，CCL21 促进了体外癌细胞诱导的淋巴细胞反应。在荷瘤小鼠中，CCL21 通过淋巴细胞抑制肿瘤生长并延长小鼠存活时间，尤其是在 CCR7+癌细胞中。此外，淋巴细胞中的 Toll 样受体 2 激活有助于 CCL21 的肿瘤抑制功能，无论是在体外还是体内。本研究表明，CCL21 提高了 CCR7+乳腺癌细胞系的免疫原性，即使在 MMC 治疗下也能触发淋巴细胞的抗肿瘤反应。这些发现为 CCL21 相关抗肿瘤反应的研究和应用提供了新的视角。
