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PD-L1 表达与 CD8 阳性淋巴细胞在人类肿瘤中的研究:一项基于 11, 838 例肿瘤样本的组织芯片研究

英文原题:PD-L1 expression and CD8 positive lymphocytes in human neoplasms: A tissue microarray study on 11,838 tumor samples.

PubMed 2023/01/01(内容时间) Cancer Biomark Q4 · IF 1.8(JCR 2025)

研究概要

PD-L1在肿瘤细胞和炎症细胞中的表达见于多种人类肿瘤类型。PD-L1阳性癌症中肿瘤浸润CD8阳性淋巴细胞的比例高于PD-L1阴性癌症,提示抗肿瘤免疫反应可能触发肿瘤PD-L1表达。

研究思路结论见上方概要

程序性死亡配体1(PD-L1)是越来越多肿瘤类型中免疫检查点抑制剂治疗的靶点,但关于PD-L1在不同癌症类型中表达的共识图景仍缺乏。

我们分析了118种人类肿瘤类型中11,838份样本的免疫组化PD-L1表达及其与肿瘤浸润CD8阳性淋巴细胞的关系。

在10%阳性肿瘤细胞的截断水平下,118种肿瘤类型中有85种(72%)观察到PD-L1阳性,包括胸腺瘤(100%阳性)、霍奇金淋巴瘤(93%)、未分化甲状腺癌(76%)、卡波西肉瘤(71%)、肉瘤样尿路上皮癌(71%),以及阴茎(67%)、宫颈(65%)、口底(61%)、肺(53%)和咽部(50%)的鳞状细胞癌。在免疫细胞中,103种(87%)肿瘤类型可检测到PD-L1阳性,包括造血和淋巴组织肿瘤(75%至100%)、腮腺Warthin瘤(95%)和Merkel细胞癌(82%)。在所有肿瘤类型中以及个别肿瘤类型中,包括卵巢浆液性癌、非特殊型浸润性乳腺癌、肠型胃腺癌和脂肪肉瘤,肿瘤细胞中PD-L1阳性与肿瘤内CD8阳性淋巴细胞数量显著相关(每项p< 0.0001)。

展开英文摘要原文

BACKGROUND: Programmed death ligand 1 (PD-L1) is the target of immune checkpoint inhibitor therapies in a growing number of tumor types, but a unanimous picture on PD-L1 expression across cancer types is lacking. MATERIALS AND METHODS: We analyzed immunohistochemical PD-L1 expression in 11,838 samples from 118 human tumor types and its relationship with tumor infiltrating CD8 positive lymphocytes. RESULTS: At a cut-off level of 10% positive tumor cells, PD-L1 positivity was seen in 85 of 118 (72%) tumor types, including thymoma (100% positive), Hodgkin's lymphoma (93%), anaplastic thyroid carcinoma (76%), Kaposi sarcoma (71%), sarcomatoid urothelial carcinoma (71%), and squamous cell carcinoma of the penis (67%), cervix (65%), floor of the mouth (61%), the lung (53%), and pharynx (50%). In immune cells, PD-L1 positivity was detectable in 103 (87%) tumor types, including tumors of haematopoetic and lymphoid tissues (75% to 100%), Warthin tumors of the parotid glands (95%) and Merkel cell carcinoma (82%). PD-L1 positivity in tumor cells was significantly correlated with the number of intratumoral CD8 positive lymphocytes across all tumor types as well as in individual tumor types, including serous carcinoma of the ovary, invasive breast carcinoma of no special type, intestinal gastric adenocarcinoma, and liposarcoma (p< 0.0001 each). CONCLUSIONS: PD-L1 expression in tumor and inflammatory cells is found in a wide range of human tumor types. Higher rates of tumor infiltrating CD8 positive lymphocytes in PD-L1 positive than in PD-L1 negative cancers suggest that the antitumor immune response may trigger tumoral PD-L1 expression.

论文信息

作者
Möller K、Knöll M、Bady E、Schmerder MJ、Rico SD、Kluth M、Hube-Magg C、Blessin NC
单位
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Germany
期刊
Cancer biomarkers : section A of Disease markers2023
原文标识
PubMed 36683495 · DOI 10.3233/CBM-220030