PD-L1 表达和 CD8 阳性淋巴细胞在人类肿瘤中的表达:对 11838 个肿瘤样本的组织微阵列研究。
PD-L1 expression and CD8 positive lymphocytes in human neoplasms: A tissue microarray study on 11,838 tumor samples.
机构信息
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany.
出版信息
Cancer Biomark. 2023;36(2):177-191. doi: 10.3233/CBM-220030.
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.
背景
程序性死亡配体 1(PD-L1)是越来越多种肿瘤类型的免疫检查点抑制剂治疗的靶点,但缺乏对癌症类型之间 PD-L1 表达的一致认识。
材料与方法
我们分析了 118 个人类肿瘤类型的 11838 个样本的免疫组化 PD-L1 表达及其与肿瘤浸润 CD8 阳性淋巴细胞的关系。
结果
在 10%肿瘤细胞阳性的截断水平下,118 种肿瘤类型中有 85 种(72%)呈 PD-L1 阳性,包括胸腺瘤(100%阳性)、霍奇金淋巴瘤(93%)、间变性甲状腺癌(76%)、卡波西肉瘤(71%)、肉瘤样尿路上皮癌(71%)和阴茎鳞状细胞癌(67%)、子宫颈(65%)、口底(61%)、肺(53%)和咽(50%)。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%)、腮腺沃辛瘤(95%)和 Merkel 细胞癌(82%)。所有肿瘤类型以及个别肿瘤类型(包括卵巢浆液性癌、非特殊型浸润性乳腺癌、胃肠腺癌和脂肪肉瘤)中,肿瘤细胞 PD-L1 阳性与肿瘤内 CD8 阳性淋巴细胞数量显著相关(p<0.0001)。
结论
肿瘤和炎症细胞中的 PD-L1 表达存在于广泛的人类肿瘤类型中。PD-L1 阳性肿瘤比 PD-L1 阴性肿瘤中浸润的 CD8 阳性淋巴细胞更高,这表明抗肿瘤免疫反应可能触发肿瘤 PD-L1 表达。