Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target,Immunopharmacology and Immunotoxicology

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Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target
Immunopharmacology and Immunotoxicology ( IF 3.3 ) Pub Date : 2020-10-26 , DOI: 10.1080/08923973.2020.1837865
Ahmad-Reza Mahmoudi _{1,

2} , Roya Ghods _{3,

4} , Azadeh Rakhshan ₅ , Zahra Madjd _{3,

4} , Mohammad-Reza Bolouri ₆ , Jafar Mahmoudian ₇ , Shaghayegh Rahdan ₈ , Mohammad-Reza Shokri ₈ , Shima Dorafshan _{3,

4} , Mehdi Shekarabi _{1,

6} , Amir-Hassan Zarnani _{1,

2,

8}

Affiliation

Abstract

Background

Melanoma has increased in incidence worldwide prompting investigators to search for new biomarkers for targeted immunotherapy of this disease. Placenta specific 1 (PLAC1) is a new member of cancer-testis antigens with widespread expression in many types of cancer. Here, we aimed to study for the first time the expression pattern of PLAC1 in skin cancer samples including cutaneous melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) in comparison to normal skin and nevus tissues and potential therapeutic effect of anti-PLAC1 antibody in melanoma cancer cell lines in vitro.

Materials and methods

Polyclonal and monoclonal antibodies were applied for immunohistochemical profiling of PLAC1 expression using tissue microarray. The cytotoxic action of anti-PLAC1 antibody alone or as an antibody drug conjugate (with anti-neoplastic agent SN38) was investigated in melanoma cell lines.

Results

We observed that 100% (39 of 39) of melanoma tissues highly expressed PLAC1 with both cytoplasmic and surface expression pattern. Investigation of PLAC1 expression in BCC (n = 110) samples showed negative results. Cancer cells in SCC samples (n = 66) showed very weak staining. Normal skin tissues and nevus samples including congenital melanocytic nevus failed to express PLAC1. Anti-PLAC1-SN38 exerted a specific pattern of cytotoxicity in a dose- and time-dependent manner in melanoma cells expressing surface PLAC1.

Conclusions

Our findings re-inforce the concept of re-expression of embryonic/placental tissue antigens in cancer and highlight the possibility of melanoma targeted therapy by employing anti-PLAC1 antibodies. The data presented here should lead to the future research on targeted immunotherapy of patients with melanoma.

中文翻译：

发现用于黑色素瘤免疫治疗的潜在生物标记物：PLAC1作为新兴靶标

摘要

背景

黑色素瘤在世界范围内的发病率上升，促使研究人员寻找新的生物标记物用于该疾病的靶向免疫治疗。胎盘特异性1（PLAC1）是癌症-睾丸抗原的新成员，在多种类型的癌症中都有广泛表达。在这里，我们旨在首次研究PLAC1在皮肤癌样品中的表达模式，包括皮肤黑素瘤，基底细胞癌（BCC），鳞状细胞癌（SCC）与正常皮肤和痣组织的比较以及抗癌的潜在治疗作用-PLAC1抗体在黑色素瘤癌细胞系中的体外作用。

材料和方法

使用组织芯片，将多克隆抗体和单克隆抗体用于PLAC1表达的免疫组化分析。在黑色素瘤细胞系中研究了抗PLAC1抗体单独或作为抗体药物偶联物（与抗肿瘤剂SN38）的细胞毒性作用。

结果

我们观察到黑色素瘤组织中有100％（39个中的39个）高表达具有细胞质和表面表达模式的PLAC1。对BCC（n = 110）样本中PLAC1表达的调查显示阴性结果。SCC样品（n = 66）中的癌细胞染色非常弱。正常皮肤组织和痣样品（包括先天性黑素细胞痣）均未表达PLAC1。抗PLAC1-SN38在表达表面PLAC1的黑素瘤细胞中以剂量和时间依赖性的方式发挥细胞毒性的特定模式。