Munn David H, Mellor Andrew L
Immunotherapy Center, Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA.
Immunol Rev. 2006 Oct;213:146-58. doi: 10.1111/j.1600-065X.2006.00444.x.
Lymph nodes that lie immediately downstream of tumors [tumor-draining lymph nodes (TDLNs)] undergo profound alterations due to the presence of the upstream tumor. The antigen-presenting cell population in TDLNs becomes modified such that tumor-derived antigens are cross-presented by host cells in a tolerizing fashion. In addition, the number and suppressor activity of regulatory T cells (Tregs) are increased in the TDLN. Emerging evidence suggests that some of these Tregs may be generated de novo against specific tumor-derived antigens, and thus they arise as a direct consequence of antigen presentation in the TDLN. Others may represent Tregs against self-antigens, which undergo preferential activation in the tolerogenic milieu of the TDLN. The TDLN thus becomes an anatomic context in which presentation of new antigens not only fails to elicit a protective immune response but also actively creates systemic tolerance. In this regard, the TDLN displays features analogous to classical immune privilege. Accumulating evidence thus suggests that the TDLNs, although small in size, may exert a profound tolerizing influence on the rest of the immune system. These mechanisms will need to be interrupted in order for clinical anti-tumor immunotherapy to be successful.
位于肿瘤紧邻下游的淋巴结[肿瘤引流淋巴结（TDLN）]会因上游肿瘤的存在而发生深刻改变。TDLN中的抗原呈递细胞群体发生改变，使得肿瘤衍生抗原以一种诱导耐受的方式由宿主细胞交叉呈递。此外，TDLN中调节性T细胞（Treg）的数量和抑制活性增加。新出现的证据表明，其中一些Treg可能是针对特定肿瘤衍生抗原重新产生的，因此它们是TDLN中抗原呈递的直接结果。其他的可能代表针对自身抗原的Treg，它们在TDLN的致耐受环境中经历优先激活。因此，TDLN成为一种解剖学环境，在其中新抗原的呈递不仅无法引发保护性免疫反应，反而会积极产生全身耐受性。在这方面，TDLN表现出与经典免疫豁免类似的特征。越来越多的证据因此表明，TDLN虽然体积小，但可能对免疫系统的其他部分产生深远的耐受影响。为了使临床抗肿瘤免疫治疗取得成功，这些机制需要被阻断。
