Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Science. 2010 May 7;328(5979):749-52. doi: 10.1126/science.1185837. Epub 2010 Mar 25.
Tumor manipulation of host immunity is important for tumor survival and invasion. Many cancers secrete CCL21, a chemoattractant for various leukocytes and lymphoid tissue inducer cells, which drive lymphoid neogenesis. CCL21 expression by melanoma tumors in mice was associated with an immunotolerant microenvironment, which included the induction of lymphoid-like reticular stromal networks, an altered cytokine milieu, and the recruitment of regulatory leukocyte populations. In contrast, CCL21-deficient tumors induced antigen-specific immunity. CCL21-mediated immune tolerance was dependent on host rather than tumor expression of the CCL21 receptor, CCR7, and could protect distant, coimplanted CCL21-deficient tumors and even nonsyngeneic allografts from rejection. We suggest that by altering the tumor microenvironment, CCL21-secreting tumors shift the host immune response from immunogenic to tolerogenic, which facilitates tumor progression.
肿瘤对宿主免疫的操纵对于肿瘤的存活和侵袭很重要。许多癌症分泌 CCL21，这是一种趋化因子，可以吸引各种白细胞和淋巴组织诱导细胞，从而驱动淋巴生成。在小鼠的黑色素瘤肿瘤中，CCL21 的表达与免疫耐受微环境相关，包括诱导淋巴样网状基质网络、细胞因子环境改变和调节性白细胞群的募集。相比之下，CCL21 缺陷型肿瘤诱导了抗原特异性免疫。CCL21 介导的免疫耐受依赖于宿主而非肿瘤表达 CCL21 受体 CCR7，并且可以保护远处共植入的 CCL21 缺陷型肿瘤，甚至非同种异体移植物免受排斥。我们认为，通过改变肿瘤微环境，分泌 CCL21 的肿瘤将宿主免疫反应从免疫原性转变为耐受性，从而促进肿瘤的进展。
