Cancer Res：转移性黑色素瘤患者在肿瘤微环境免疫细胞被激活

在许多类型的癌症中，激活的免疫细胞会促进浸润肿瘤，影响临床疗效。但这些细胞在何处被激活并不总是很清楚，最近发表在Cancer Research杂志上的一则研究表明在转移性黑色素瘤患者中，在肿瘤微环境免疫细胞是被激活的。

在我们开始我们的研究之前，一直认为免疫反应主要在淋巴结中被触发。淋巴细胞是一个重要的免疫细胞集，一旦成为激活状态后可通过血液迁移到肿瘤部位。研究结果表明在肿瘤微环境存在激活未成熟的淋巴细胞的替代路径。这样的基本知识是至关重要的，因为我们设法了解肿瘤如何逃避抗肿瘤免疫反应，我们如何才能开发办法来对付这种肿瘤细胞逃避免疫。

对于大多数保护我们身体的免疫反应抵抗例如入侵的微生物，淋巴细胞活化的主要场所是淋巴结、脾脏和黏膜相关淋巴组织。所有这些网络都致力于启动和维持免疫反应。然而，在某些情况下，慢性感染例如丙型肝炎病毒、异位淋巴结构或淋巴结构会成为感染部位，局部帮助针对传染性病原体的淋巴细胞产生免疫反应。

异位淋巴结构也已观察到在某些恶性肿瘤中存在包括乳腺癌、肺癌和大肠肿瘤，但在黑色素瘤中并未观察到。在一些研究中，他们的存在已被证实与改善预后相关。Van Baren和他的同事观察到出29名黑色素瘤皮肤转移患者中有七名患者存在异位淋巴结构。相比之下，原发性黑色素瘤样本中并不含有完整的异位淋巴结构。

事实上，研究人员发现淋巴结构存在于皮肤转移患者中，而在原发肿瘤患者中并不存在，这一点是非常有趣的，他们认为理解这种差异的原因将有助确定在黑色素病情恶化中抗黑色素瘤免疫反应是如何发挥作用的。

编译自：Immune responses can be generated locally within human melanoma skin metastases

doi:10.1158/0008-5472.CAN-12-1377
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Neogenesis of Lymphoid Structures and Antibody Responses Occur in Human Melanoma Metastases

Arcadi Cipponi1, Marjorie Mercier1, Teofila Seremet1, Jean-Fran?ois Baurain5, et al.

Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible.