研究概要
本研究表明,在东印度队列的CRC中,PD-L1的频率相对较低。本研究中的免疫细胞浓度是使用基于图像分析的客观化方法计算的。肿瘤细胞中PD-L1表达与肿瘤浸润免疫细胞的显著相关性表明其在CRC病理生物学中的关键作用,特别是通过调节TIME。考虑到PD-L1在多种恶性肿瘤中的治疗意义,它可能是部分病例的关键治疗靶点之一。
研究思路结论见上方概要
方法
这是一项基于医院的横断面观察性研究。PD-L1表达在蛋白质水平通过免疫组织化学评估,在mRNA水平通过qRT-PCR评估。免疫细胞标志物(CD4、CD8、CD20、FOXP3和CD163)使用ImageJ Fiji平台进行判读。
结果
在104例病例中,21%为PD-L1阳性,且在右侧CRC中更为常见。PD-L1阳性病例显示所有T细胞亚群(CD4+、CD8+和FOXP3+)浓度显著更高,并观察到CD20+ B细胞和CD163+巨噬细胞。PD-L1表达与临床特征、病理亚型、分级或分期、错配修复状态(熟练 vs 缺陷)以及生存之间未见统计学显著性。
展开英文摘要原文
INTRODUCTION/BACKGROUND: Colorectal carcinoma (CRC) is a common malignancy, with its diverse clinical, pathological, and molecular features. The immune microenvironment of a tumor comprises of interplay between various cells and molecules, and has a significant role in deciding the tumor behavior and overall prognosis. PD-L1 (programmed cell death ligand-1) has been implicated in the regulation of the tumor immune microenvironment (TIME). There is limited data regarding the correlation of PD-L1 expression with immune cell profile in CRCs, especially in the Indian setting. The study aimed to assess the PD-L1 expression in CRC tumor cells and its association with TIME, mismatch repair (MMR), and various other clinicopathological parameters.
METHODS: This is a hospital-based, cross-sectional observational study. PD-L1 expression was assessed at the protein level by immunohistochemistry and mRNA level by qRT-PCR. Immune cell markers (CD4, CD8, CD20, FOXP3, and CD163) were interpreted using the ImageJ Fiji platform.
RESULTS: Of the 104 cases, 21% were PD-L1 positive and were more common in right-sided CRCs. PD-L1 positive cases showed significantly higher concentrations of all T-cell subsets (CD4+ , CD8+ , and FOXP3+), CD20+ B-cells, and CD163+ macrophages were noted. No statistical significance was seen between PD-L1 expression with clinical profile, pathological subtype, grade or stage, mismatch repair status (proficient vs deficient), and survival.
CONCLUSIONS: The present study showed a relatively lower frequency of PD-L1 in CRC from the Eastern Indian cohort. The immune cell concentration in the present study was calculated using image analysis-based objectivised methods. Significant correlation of PD-L1 expression in tumor cells with the tumor-infiltrating immune cells indicated its crucial role in the pathobiology of CRC especially by regulating the TIME. Considering the therapeutic implication of PD-L1 in various malignancies, it may be one of the crucial therapeutic targets in a proportion of cases.
论文信息
- 作者
- Shahin M、Patra S、Purkait S、Kar M、Das Majumdar SK、Mishra TS、Samal SC、Nayak HK
- 第一作者单位
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.India
- 通讯作者单位
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. wususama@gmail.com.India
- 文献类型
- 观察性研究
- 期刊
- Journal of gastrointestinal cancer2024 Jun