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黑色素瘤过继性免疫治疗的组织预后标志物。

Tissue prognostic markers for adoptive immunotherapy in melanoma.

作者信息

Quereux Gaëlle, Pandolfino Marie-Christine, Knol Anne-Chantal, Khammari Amir, Volteau Christelle, Nguyen Jean-Michel, Dreno Brigitte

机构信息

Unit of Skin Oncology, CHU, Place A. Ricordeau, 44035 Nantes, France.

出版信息

Eur J Dermatol. 2007 Jul-Aug;17(4):295-301. doi: 10.1684/ejd.2007.0203. Epub 2007 Jun 1.

Abstract

Adoptive immunotherapy for melanoma appears to be a promising approach. The aim of our study was to discuss the role of "tumour tissue" immunogenicity in response to adoptive immunotherapy. We thus studied the potential correlation between the expression of some melanocyte differentiation antigens, adhesion molecules and cytokines expressed by the tumour cells and the survival of patients receiving an adoptive immunotherapy with autologous Tumour Infiltrating Lymphocytes (TIL). An immunohistochemical study was performed on the lymph node samples obtained from 38 patients who received autologous TIL plus interleukin-2. Frozen sections were immunostained for melanocyte differentiation antigens (Melan-A and gp100), MHC molecules (Class I and II), adhesion molecules (ICAM-1, LFA-3) and suppressive cytokines (IL-10, TGF-beta and alpha-MSH). Expression levels of each marker were evaluated using a semi-quantitative visual scale. Using a multivariate analysis, a low expression level of TGF-beta by tumour cells was significantly associated with a prolonged relapse-free survival. A low expression level of TGF-beta, IL-10, ICAM-1 and alpha-MSH by tumour cells was significantly associated with a longer overall survival. This work suggests that a weak expression of immunosuppressive cytokines (IL-10, TGF-beta and alpha-MSH) could be a favourable prognostic marker for patients receiving autologous TIL.

摘要

黑色素瘤的过继性免疫疗法似乎是一种很有前景的方法。我们研究的目的是探讨“肿瘤组织”免疫原性在过继性免疫疗法反应中的作用。因此,我们研究了肿瘤细胞表达的一些黑素细胞分化抗原、黏附分子和细胞因子的表达与接受自体肿瘤浸润淋巴细胞(TIL)过继性免疫疗法患者生存率之间的潜在相关性。对38例接受自体TIL加白细胞介素-2治疗患者的淋巴结样本进行了免疫组织化学研究。冰冻切片对黑素细胞分化抗原(Melan-A和gp100)、MHC分子(I类和II类)、黏附分子(ICAM-1、LFA-3)和抑制性细胞因子(IL-10、TGF-β和α-MSH)进行免疫染色。使用半定量视觉量表评估每个标志物的表达水平。通过多变量分析,肿瘤细胞中TGF-β低表达水平与无复发生存期延长显著相关。肿瘤细胞中TGF-β、IL-10、ICAM-1和α-MSH低表达水平与总生存期延长显著相关。这项研究表明,免疫抑制细胞因子(IL-10、TGF-β和α-MSH)弱表达可能是接受自体TIL治疗患者的一个有利预后标志物。

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