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免疫检查点调节因子细胞毒性T淋巴细胞相关抗原4(CTLA-4)和程序性细胞死亡蛋白配体1(PD-L1)在乳腺浸润性导管癌中的表达

Expression of Immune Checkpoint Regulator Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) and Programmed Cell Death Protein Ligand 1 (PD-L1) in Invasive Ductal Carcinoma Breast.

作者信息

Diwaker Preeti, Jha Tanvi, Gogoi Priyanka, Arora Vinod Kumar, Ansari Mohammad Ahmad, Kaur Navneet

机构信息

Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India.

Multi-Disciplinary Research Unit, University College of Medical Sciences and GTB Hospital, Delhi, 110095 India.

出版信息

Indian J Surg Oncol. 2024 Dec;15(4):713-720. doi: 10.1007/s13193-024-01977-z. Epub 2024 Jun 13.

DOI:10.1007/s13193-024-01977-z
PMID:39555338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11564441/
Abstract

Despite significant advancement in the diagnostic and therapeutic aspects of breast carcinoma, the prognosis remains dismal. Recently, with advances in its understanding, various immune system-based management strategies have been developed. CTLA-4 suppresses lymphocyte reactivity, IL-2 secretion, and IL-2 receptor expression and triggers cell cycle arrest. PD-L1 inhibits the proliferation and cytotoxicity of T cells and inhibits release of cytokines. Hence, we planned to evaluate the immunoexpression of CTLA-4 and PD-L1 in invasive ductal carcinoma breast and seek correlation between their immunopositivity and the clinicopathological parameters. This was a retrospective study conducted on archival material of 50 cases of breast carcinoma tissue microarrays. Clinicopathological details were recorded. All cases were evaluated for immunohistochemical expression of CTLA-4 and PD-L1. Cytoplasmic expression of CTLA-4 and membranous expression of PD-L1 were considered positive and staining intensity was recorded as mild, moderate, and intense. Data was recorded and analyzed. Immunopositivity for CTLA-4 was seen in 92% of cases of breast carcinoma. CTLA-4 staining intensity showed significant association with TNM staging of breast carcinomas ( = 0.036). Age group of the breast carcinoma cases showed a statistically significant correlation with PD-L1 immunoexpression ( = 0.002). No significant correlation was found between all other clinicopathological characteristics and CTLA-4 or PD-L1 immunostaining. Our study shows that CTLA-4 is a more important immune checkpoint regulator in breast carcinomas in comparison to PD-L1. Thus, anti-CTLA-4 immunotherapy might prove to be of immense help in the treatment of invasive ductal carcinoma breast showing overexpression of CTLA-4.

摘要

尽管在乳腺癌的诊断和治疗方面取得了显著进展,但其预后仍然不佳。最近,随着对其认识的不断深入,已开发出各种基于免疫系统的管理策略。CTLA-4抑制淋巴细胞反应性、IL-2分泌和IL-2受体表达,并触发细胞周期停滞。PD-L1抑制T细胞的增殖和细胞毒性,并抑制细胞因子的释放。因此,我们计划评估CTLA-4和PD-L1在乳腺浸润性导管癌中的免疫表达,并寻找它们的免疫阳性与临床病理参数之间的相关性。这是一项对50例乳腺癌组织微阵列存档材料进行的回顾性研究。记录了临床病理细节。对所有病例进行CTLA-4和PD-L1的免疫组织化学表达评估。CTLA-4的细胞质表达和PD-L1的膜性表达被视为阳性,并将染色强度记录为轻度、中度和重度。记录并分析数据。在92%的乳腺癌病例中观察到CTLA-4免疫阳性。CTLA-4染色强度与乳腺癌的TNM分期显示出显著相关性(=0.036)。乳腺癌病例的年龄组与PD-L1免疫表达显示出统计学上的显著相关性(=0.002)。在所有其他临床病理特征与CTLA-4或PD-L1免疫染色之间未发现显著相关性。我们的研究表明,与PD-L1相比,CTLA-4在乳腺癌中是更重要的免疫检查点调节因子。因此,抗CTLA-4免疫疗法可能对治疗显示CTLA-4过表达乳腺浸润性导管癌有巨大帮助。

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本文引用的文献

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PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences Are Emerging. A Literature Review.乳腺癌中的PD-1/PD-L1靶向治疗:首批临床证据正在浮现。文献综述。
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Cancer Cell-Intrinsic PD-1 and Implications in Combinatorial Immunotherapy.肿瘤细胞内在的 PD-1 及其在联合免疫治疗中的意义。
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PD-1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Large B-cell Richter Transformation (DLBCL-RT): A Characteristic Feature of DLBCL-RT and Potential Surrogate Marker for Clonal Relatedness.PD-1 在慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 (CLL/SLL) 和大 B 细胞 Richter 转化 (DLBCL-RT) 中的表达:DLBCL-RT 的特征性特征和潜在的克隆相关性替代标志物。
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