Preynat-Seauve Olivier, Contassot Emmanuel, Schuler Prisca, Piguet Vincent, French Lars E, Huard Bertrand
Louis Jeantet Skin Cancer Laboratory, Department of Dermatology, University Medical Center, Geneva, Switzerland.
Cancer Res. 2007 May 15;67(10):5009-16. doi: 10.1158/0008-5472.CAN-06-4494.
Metastases often develop in lymphoid organs. However, the immunologic mechanism allowing such invasion is not known because these organs are considered to be hostile to tumor cells. Here, we analyzed the interactions between tumor cells and CD8(+) T cells in such lymphoid organs. Tumor cells implanted into lymph nodes were able to induce tumor-specific cytotoxic CD8(+) T-cell responses, conducting to tumor rejection, in contrast to primary extralymphatic tumors rapidly anergizing T cells in draining lymph nodes (DLN) via a cross-presentation process. This abortive CD8(+) T-cell response to extralymphatic tumor is independent of the subcellular localization of antigen in tumor cells and is consistent with a lack of CD4(+) T-cell help. Notably, this anergy was potent enough to allow successful DLN implantation of tumor cells. Such distant cross-tolerization of tumor-specific CD8(+) T cells may be a determinant permissive event leading to invasion of DLN. In this situation, metastatic tumor cells do not need to down-regulate their immunogenicity to spread.
转移灶常发生于淋巴器官。然而，尚不清楚允许这种侵袭的免疫机制，因为这些器官被认为对肿瘤细胞具有敌意。在此，我们分析了肿瘤细胞与此类淋巴器官中CD8(+) T细胞之间的相互作用。与原发于淋巴外的肿瘤通过交叉呈递过程迅速使引流淋巴结（DLN）中的T细胞失能不同，植入淋巴结的肿瘤细胞能够诱导肿瘤特异性细胞毒性CD8(+) T细胞反应，从而导致肿瘤排斥。这种对淋巴外肿瘤的CD8(+) T细胞反应失败与肿瘤细胞中抗原的亚细胞定位无关，且与缺乏CD4(+) T细胞辅助一致。值得注意的是，这种失能作用强大到足以使肿瘤细胞成功植入DLN。肿瘤特异性CD8(+) T细胞的这种远距离交叉耐受可能是导致DLN侵袭的决定性允许事件。在这种情况下，转移性肿瘤细胞无需下调其免疫原性即可扩散。
