PD-L1 Expression in Colorectal Carcinoma Correlates with the Immune Microenvironment.

IF 1.6 Q4 ONCOLOGY Journal of Gastrointestinal Cancer Pub Date : 2024-06-01 Epub Date: 2024-03-26 DOI:10.1007/s12029-024-01049-z

Mohammed Shahin, Susama Patra, Suvendu Purkait, Madhabananda Kar, Saroj Kumar Das Majumdar, Tushar Subhadarshan Mishra, Subash Chandra Samal, Hemanta Kumar Nayak

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Abstract

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.

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结直肠癌中的 PD-L1 表达与免疫微环境有关

导言/背景：结直肠癌（CRC）是一种常见的恶性肿瘤，其临床、病理和分子特征各不相同。肿瘤的免疫微环境包括各种细胞和分子之间的相互作用，在决定肿瘤行为和整体预后方面起着重要作用。PD-L1（程序性细胞死亡配体-1）与肿瘤免疫微环境的调节有关（TIME）。有关 PD-L1 表达与 CRC 免疫细胞特征相关性的数据很有限，尤其是在印度环境中。本研究旨在评估 PD-L1 在 CRC 肿瘤细胞中的表达及其与 TIME、错配修复（MMR）和其他各种临床病理参数的关系：这是一项基于医院的横断面观察性研究。方法：这是一项以医院为基础的横断面观察性研究，通过免疫组织化学法评估 PD-L1 在蛋白水平的表达，通过 qRT-PCR 评估 mRNA 水平的表达。免疫细胞标记物（CD4、CD8、CD20、FOXP3 和 CD163）使用 ImageJ Fiji 平台进行解读：结果：在104个病例中，21%为PD-L1阳性，在右侧CRC中更为常见。PD-L1 阳性病例的所有 T 细胞亚群（CD4+、CD8+ 和 FOXP3+）、CD20+ B 细胞和 CD163+ 巨噬细胞的浓度都明显较高。PD-L1的表达与临床特征、病理亚型、分级或分期、错配修复状态（熟练与缺陷）以及存活率之间没有统计学意义：本研究显示，印度东部队列中的 CRC 中 PD-L1 的频率相对较低。本研究中的免疫细胞浓度是通过基于图像分析的客观化方法计算得出的。肿瘤细胞中 PD-L1 的表达与肿瘤浸润免疫细胞之间存在显著相关性，这表明 PD-L1 在 CRC 的病理生物学中发挥着关键作用，尤其是通过调节 TIME。考虑到 PD-L1 在各种恶性肿瘤中的治疗作用，它可能是部分病例的重要治疗靶点之一。

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来源期刊

Journal of Gastrointestinal Cancer ONCOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

121

期刊介绍： The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.