Gene and Protein Expression of MAGE and Associated Immune Landscape Elements in Non-Small-Cell Lung Carcinoma and Urothelial Carcinomas.

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Journal of Immunotherapy Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI:10.1097/CJI.0000000000000538
Izak Faiena, Sabina Adhikary, Colleen Schweitzer, Stephanie H Astrow, Tristan Grogan, Samuel A Funt, Adrian Bot, Tanya Dorff, Jonathan E Rosenberg, David A Elashoff, Allan J Pantuck, Alexandra Drakaki
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引用次数: 0

Abstract

Melanoma-associated antigen-A (MAGE-A) is expressed in multiple cancers with restricted expression in normal tissue. We sought to assess the MAGE-A3/A6 expression profile as well as immune landscape in urothelial (UC) and non-small cell lung carcinoma (NSCLC). We also assessed co-expression of immune-associated markers, including programmed cell death ligand 1 (PD-L1) in tumor and/or immune cells, and assessed the effect of checkpoint inhibitor treatment on these markers in the context of urothelial carcinoma. We used formalin-fixed paraffin-embedded (FFPE) tissue sections from a variety of tumor types were screened by IHC for MAGE-A and PD-L1 expression. Gene expression analyses by RNA sequencing were performed on RNA extracted from serial tissue sections. UC tumor samples from patients treated with checkpoint inhibitors were assessed by IHC and NanoString gene expression analysis for MAGE-A and immune marker expression before and after treatment. Overall, 84 samples (57%) had any detectable MAGE-A expression. Detectable MAGE-A expression was present at similar frequencies in both tumor tissue types, with 41 (50%) NSCLC and 43 (64%) UC. MAGE-A expression was not significantly changed before and after checkpoint inhibitor therapy by both IHC and NanoString mRNA sequencing. Other immune markers were similarly unchanged post immune checkpoint inhibitor therapy. Stable expression of MAGE-A3/A6 pre and post checkpoint inhibitor treatment indicates that archival specimens harvested after checkpoint therapy are applicable to screening potential candidates for MAGE therapies.

非小细胞肺癌和尿道癌中 MAGE 及相关免疫景观元素的基因和蛋白表达
黑色素瘤相关抗原-A(MAGE-A)在多种癌症中均有表达,但在正常组织中表达有限。我们试图评估 MAGE-A3/A6 的表达情况以及尿路上皮癌(UC)和非小细胞肺癌(NSCLC)的免疫状况。我们还评估了免疫相关标记物的共同表达,包括肿瘤和/或免疫细胞中的程序性细胞死亡配体 1 (PD-L1),并评估了检查点抑制剂治疗对这些标记物在尿路癌中的影响。我们使用福尔马林固定石蜡包埋(FFPE)的组织切片,通过 IHC 检测 MAGE-A 和 PD-L1 的表达。从连续组织切片中提取的 RNA 通过 RNA 测序进行了基因表达分析。通过 IHC 和 NanoString 基因表达分析评估了接受检查点抑制剂治疗的 UC 肿瘤样本在治疗前后的 MAGE-A 和免疫标记物表达情况。总体而言,84 份样本(57%)有可检测到的 MAGE-A 表达。可检测到的 MAGE-A 表达在两种肿瘤组织类型中出现的频率相似,NSCLC 为 41 例(50%),UC 为 43 例(64%)。通过IHC和NanoString mRNA测序,MAGE-A的表达在检查点抑制剂治疗前后没有明显变化。其他免疫标记物在免疫检查点抑制剂治疗后同样没有变化。MAGE-A3/A6在检查点抑制剂治疗前后的稳定表达表明,检查点治疗后采集的档案标本适用于筛选潜在的MAGE疗法候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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