在許多類型的癌癥中,，激活的免疫細胞會促進浸潤腫瘤,，影響臨床療效。但這些細胞在何處被激活并不總是很清楚,，最近發(fā)表在Cancer Research雜志上的一則研究表明在轉(zhuǎn)移性黑色素瘤患者中,，在腫瘤微環(huán)境免疫細胞是被激活的,。
在我們開始我們的研究之前，一直認(rèn)為免疫反應(yīng)主要在淋巴結(jié)中被觸發(fā),。淋巴細胞是一個重要的免疫細胞集,，一旦成為激活狀態(tài)后可通過血液遷移到腫瘤部位。研究結(jié)果表明在腫瘤微環(huán)境存在激活未成熟的淋巴細胞的替代路徑,。這樣的基本知識是至關(guān)重要的,，因為我們設(shè)法了解腫瘤如何逃避抗腫瘤免疫反應(yīng)，我們?nèi)绾尾拍荛_發(fā)辦法來對付這種腫瘤細胞逃避免疫,。
對于大多數(shù)保護我們身體的免疫反應(yīng)抵抗例如入侵的微生物,，淋巴細胞活化的主要場所是淋巴結(jié)、脾臟和黏膜相關(guān)淋巴組織,。所有這些網(wǎng)絡(luò)都致力于啟動和維持免疫反應(yīng),。然而，在某些情況下,，慢性感染例如丙型肝炎病毒、異位淋巴結(jié)構(gòu)或淋巴結(jié)構(gòu)會成為感染部位,，局部幫助針對傳染性病原體的淋巴細胞產(chǎn)生免疫反應(yīng),。
異位淋巴結(jié)構(gòu)也已觀察到在某些惡性腫瘤中存在包括乳腺癌、肺癌和大腸腫瘤,，但在黑色素瘤中并未觀察到,。在一些研究中，他們的存在已被證實與改善預(yù)后相關(guān),。Van Baren和他的同事觀察到出29名黑色素瘤皮膚轉(zhuǎn)移患者中有七名患者存在異位淋巴結(jié)構(gòu),。相比之下，原發(fā)性黑色素瘤樣本中并不含有完整的異位淋巴結(jié)構(gòu),。
事實上,，研究人員發(fā)現(xiàn)淋巴結(jié)構(gòu)存在于皮膚轉(zhuǎn)移患者中，而在原發(fā)腫瘤患者中并不存在,，這一點是非常有趣的，他們認(rèn)為理解這種差異的原因?qū)⒂兄_定在黑色素病情惡化中抗黑色素瘤免疫反應(yīng)是如何發(fā)揮作用的,。 （生物谷：Bioon.com）
編譯自：Immune responses can be generated locally within human melanoma skin metastases
doi:10.1158/0008-5472.CAN-12-1377
PMC:
PMID:
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.
