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CD73在人类转移性黑色素瘤中的表达及临床意义

CD73 expression and clinical significance in human metastatic melanoma.

作者信息

Monteiro Inês, Vigano Selena, Faouzi Mohamed, Treilleux Isabelle, Michielin Olivier, Ménétrier-Caux Christine, Caux Christophe, Romero Pedro, de Leval Laurence

机构信息

Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.

Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

出版信息

Oncotarget. 2018 Jun 1;9(42):26659-26669. doi: 10.18632/oncotarget.25426.

DOI:10.18632/oncotarget.25426
PMID:29928476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6003551/
Abstract

BACKGROUND

CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target.

RESULTS

CD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy.

CONCLUSIONS

Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients.

METHODS

CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1-3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage).

摘要

背景

CD73是一种参与腺苷生成的胞外酶。它发挥免疫抑制和促肿瘤作用,并已成为一种潜在的免疫肿瘤学靶点。

结果

在54%的黑色素瘤转移灶的肿瘤细胞(TC)中检测到CD73表达,大多数病例中TC的表达率<50%,强度各异。CD73表达与原发灶较低的Breslow深度显著相关,且在接受过非手术治疗的患者中更常见。在一项校正分析中,TC中CD73表达(H评分>37.5或强度>1)与活检后的总生存期(OS)降低显著相关。在含有肿瘤浸润单核细胞(TIMC)的样本中,35%呈现CD73阳性的TIMC。高浸润性肿瘤更有可能含有CD73阳性的TIMC。TIMC中CD73表达(百分比≥1%)与活检后的OS改善显著相关。

结论

免疫组织化学检测到超过一半的转移性黑色素瘤中存在CD73表达。虽然TC中CD73表达与OS降低显著相关,但TIMC中CD73表达与OS改善显著相关。这些结果鼓励对转移性黑色素瘤患者进行抗CD73治疗的研究。

方法

通过免疫组织化学评估114例患者转移性黑色素瘤中的CD73表达。对肿瘤细胞(TC)(百分比、强度(1 - 3)和H评分)以及肿瘤浸润单核细胞(TIMC)(百分比)的免疫染色进行评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/c5409a05530e/oncotarget-09-26659-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/2210dc1f108a/oncotarget-09-26659-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/c1341ec68a1b/oncotarget-09-26659-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/f342b17d0560/oncotarget-09-26659-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/c5409a05530e/oncotarget-09-26659-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/2210dc1f108a/oncotarget-09-26659-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/c1341ec68a1b/oncotarget-09-26659-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/f342b17d0560/oncotarget-09-26659-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb4/6003551/c5409a05530e/oncotarget-09-26659-g004.jpg

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