Johansson Junko, Siarov Jan, Kiffin Roberta, Mölne Johan, Mattsson Jan, Naredi Peter, Olofsson Bagge Roger, Martner Anna, Lindnér Per
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
Oncoimmunology. 2020 Dec 10;9(1):1854519. doi: 10.1080/2162402X.2020.1854519.
Uveal melanoma is a malignant tumor of the eye that often metastasizes to the liver conferring poor prognosis. When comparing immune profiles in peripheral blood of untreated patients with uveal melanoma liver metastasis and healthy blood donors, it was observed that immune cells of uveal melanoma patients carried immunosuppressive features. Patient blood contained an increased content of CD14HLA-DR M-MDSCs and inflammatory CD16 monocytes, while their dendritic cells expressed lower levels of activation markers. Melanoma patients also harbored an enhanced fraction of CD4Foxp3 regulatory T cells, while their effector T cells expressed lower levels of the activation marker HLA-DR. Biopsies from liver metastases were obtained from patients with uveal melanoma that subsequently underwent hyperthermic isolated hepatic perfusion (IHP) with melphalan. There were trends indicating a positive correlation between a high infiltration of CD8 T cells in metastases and an activated immune cell profile in blood. High metastatic infiltration of CD8 T cells and CD68 macrophages, but not of immunosuppressive CD163 macrophages, correlated to a longer overall survival in patients treated with IHP. Hence, while the immune system of patients with uveal melanoma shows signs of immunosuppression, the presence of activated immune cells may correlate to a longer survival, at least following IHP treatment.
葡萄膜黑色素瘤是一种眼部恶性肿瘤，常转移至肝脏，预后较差。在比较未经治疗的葡萄膜黑色素瘤肝转移患者与健康献血者外周血中的免疫特征时，发现葡萄膜黑色素瘤患者的免疫细胞具有免疫抑制特性。患者血液中CD14HLA - DR M - MDSCs和炎性CD16单核细胞含量增加，而其树突状细胞表达的活化标志物水平较低。黑色素瘤患者还具有较高比例的CD4Foxp3调节性T细胞，而其效应T细胞表达的活化标志物HLA - DR水平较低。从接受美法仑热灌注隔离肝灌注（IHP）的葡萄膜黑色素瘤患者获取肝转移灶活检组织。有趋势表明转移灶中CD8 T细胞的高浸润与血液中活化免疫细胞谱呈正相关。CD8 T细胞和CD68巨噬细胞的高转移浸润，而非免疫抑制性CD163巨噬细胞的浸润，与接受IHP治疗患者的总生存期延长相关。因此，虽然葡萄膜黑色素瘤患者的免疫系统显示出免疫抑制迹象，但活化免疫细胞的存在可能与更长的生存期相关，至少在IHP治疗后如此。
