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CD8 淋巴细胞表型在具有不同 CDKN2A 突变状态的原发性多发性和家族性黑色素瘤中的意义。

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.

机构信息

Department of Dermatovenerology, "Elias" Emergency University Hospital, 011461 Bucharest, Romania.

Institute of Doctoral Studies, Doctoral School of Medicine, "Ovidius" University of Constanţa, 900573 Constanţa, Romania.

出版信息

Medicina (Kaunas). 2023 Dec 12;59(12):2151. doi: 10.3390/medicina59122151.

DOI:10.3390/medicina59122151
PMID:38138255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10744472/
Abstract

: In the realm of the rising incidence of cutaneous and mucous melanoma, CDKN2A mutations characterize familial and multiple primary melanoma cases. The involvement of tumor-infiltrating lymphocytes (TILs) is interconnected with survival rates, but may extend even further. The aim of this study is to verify the accuracy of the classical "naked eye" count of CD8-positive T cells comprised within the tumoral population and peritumoral infiltrate versus that obtained via a special software run by the aid of artificial intelligence (AI), used to determine the percentage of CD8-positive TILs. : The present retrospective cross-sectional study conducted over a period of 5 years (2018-2022) focused on patients diagnosed with mucous and/or cutaneous melanoma, with a positive family history for melanoma, or personal antecedents of primary malignant melanocytic lesions. The 23 selected cases were diagnosed histopathologically, tested for CDKN2A mutations through fluorescent hybridization in situ, and CD8 immunohistochemistry was performed. The included slides were evaluated both manually (naked-eye examination) and automatically (via QuPath platform) for quantifying the CD8-positive TILs. : The number of CD8-positive TILs in melanoma samples has been more accurately identified through the use of an AI-mediated software as compared to the human-eye evaluation performed by experimental pathologists. A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. : The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

摘要

: 在皮肤和黏膜黑色素瘤发病率上升的情况下,CDKN2A 突变是家族性和多发性原发性黑色素瘤病例的特征。肿瘤浸润淋巴细胞 (TILs) 的参与与生存率相关,但可能更为广泛。本研究旨在验证经典的“肉眼”计数肿瘤内和肿瘤周围浸润的 CD8 阳性 T 细胞与通过人工智能 (AI) 辅助的特殊软件获得的计数的准确性,该软件用于确定 CD8 阳性 TIL 的百分比。 : 本回顾性横断面研究在 5 年期间(2018-2022 年)进行,重点关注诊断为黏膜和/或皮肤黑色素瘤、有黑色素瘤阳性家族史或原发性恶性黑色素瘤病变个人史的患者。23 例选定病例通过组织病理学诊断、荧光原位杂交检测 CDKN2A 突变,并进行 CD8 免疫组织化学染色。包含的幻灯片既通过手动(肉眼检查)也通过自动(通过 QuPath 平台)进行评估,以定量 CD8 阳性 TILs。 : 与实验病理学家进行的肉眼评估相比,使用人工智能介导的软件可以更准确地识别黑色素瘤样本中 CD8 阳性 TILs 的数量。与基质淋巴细胞相比,肿瘤内 CD8 阳性淋巴细胞的比例越高,与更多的转移性部位呈正相关。 : CD8 淋巴细胞表型在家族性和多发性原发性黑色素瘤中具有重要意义,并且可能是一种具有成本效益的研究,可以帮助确定黑色素瘤的预后和对免疫治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc27/10744472/2e1dc71079bc/medicina-59-02151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc27/10744472/f056b4b73675/medicina-59-02151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc27/10744472/2e1dc71079bc/medicina-59-02151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc27/10744472/f056b4b73675/medicina-59-02151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc27/10744472/2e1dc71079bc/medicina-59-02151-g002.jpg

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本文引用的文献

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Nicotinamide Inhibits T Cell Exhaustion and Increases Differentiation of CD8 Effector T Cells.烟酰胺抑制T细胞耗竭并增加CD8效应T细胞的分化。
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Comprehensive Analysis Revealed that is a Biomarker for Immune Infiltrates in Multiple Cancers.
综合分析表明, 是多种癌症中免疫浸润的生物标志物。
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Different Response to Immunotherapy According to Melanoma Histologic Subtype.黑色素瘤组织学亚型对免疫疗法的不同反应。
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The association between CD8+ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis.CD8+肿瘤浸润淋巴细胞与癌症免疫治疗临床结局的关联:一项系统评价与荟萃分析。
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9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy.9p21 缺失导致肿瘤免疫微环境寒冷,并对免疫检查点治疗产生原发性耐药。
Nat Commun. 2021 Sep 23;12(1):5606. doi: 10.1038/s41467-021-25894-9.
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Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients.CD8+T 细胞浸润相关标志物的开发和验证用于黑色素瘤患者。
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