NY-ESO-1表达的脂肪细胞和神经源性组织芯片综合分析——恶性外周神经鞘瘤和脂肪肉瘤中有前景的免疫治疗靶点
Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma.
作者信息
Shurell Elizabeth, Vergara-Lluri Maria E, Li Yunfeng, Crompton Joseph G, Singh Arun, Bernthal Nicholas, Wu Hong, Eilber Fritz C, Dry Sarah M
机构信息
Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA.
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
出版信息
Oncotarget. 2016 Nov 8;7(45):72860-72867. doi: 10.18632/oncotarget.12096.
BACKGROUND
Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored.
RESULTS
NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings.
CONCLUSIONS
We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.
背景
靶向癌胚抗原NY-ESO-1的免疫疗法对放化疗反应不佳的肿瘤显示出前景。恶性外周神经鞘瘤（MPNST）和脂肪肉瘤（LPS）具有化疗抗性，且有效治疗选择较少。材料与方法：利用包含原发性、复发性和转移性样本中良性及恶性肿瘤的综合组织微阵列（TMA），我们检测了外周神经鞘瘤（PNST）和脂肪细胞性肿瘤中NY-ESO-1的表达。PNST TMA包括42例MPNST（自发的n = 26，与NF1相关的n = 16）、35例神经纤维瘤（自发的n = 22，与NF-1相关的n = 13）、11例神经鞘瘤和18条正常神经。LPS TMA包括48例高分化/去分化（WD/DD）LPS、13例黏液样/圆形细胞LPS)、3例多形性LPS、8例脂肪瘤、1例髓脂肪瘤和3例正常脂肪细胞组织样本。进行一式三份染色后，对NY-ESO-1的强度和密度进行评分。
结果
NY-ESO-1表达仅见于恶性肿瘤。100%的黏液样/圆形细胞LPS显示NY-ESO-1表达，而只有6%的WD/DD LPS显示蛋白表达，其中1例为WD LPS。在MPNST中，4/26（15%）的自发型和2/16（12%）的与NF1相关的MPNST显示NY-ESO-1表达。在原发性、新辅助治疗和转移性情况下，黏液样/圆形细胞和去分化LPS以及MPNST中观察到强NY-ESO-1表达。
结论
我们发现MPNST中NY-ESO-1表达的发生率高于先前报道，突出了可能从免疫疗法中获益的MPNST患者亚组。本研究扩展了我们对WD/DD LPS中NY-ESO-1的理解，并且是首次在WD LPS以及转移性/复发性黏液样/圆形细胞LPS中进行染色的证明。这些结果表明，靶向NY-ESO-1的免疫疗法可能使对传统疗法耐药的侵袭性肿瘤患者受益。
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