免疫功能正常与免疫抑制患者皮肤鳞状细胞癌中 PD-L1、B7-H3 和 PD-1 的表达。
PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma.
机构信息
University of Maryland Greenebaum Comprehensive Cancer Center, 22 South Greene Street Room N9E29, Baltimore, MD, 21201, USA.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
出版信息
Cancer Immunol Immunother. 2018 May;67(5):805-814. doi: 10.1007/s00262-018-2138-8. Epub 2018 Feb 27.
BACKGROUND
To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status.
METHODS
We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%).
RESULTS
Of 66 cases, 42 were immunocompetent, 24 immunosuppressed (13 organ transplant, 8 HIV+, 3 other). Defining positive expression at > 5%, 26% of tumors were positive for PD-L1, 85% for B7-H3, 80% had CD8 T cells that expressed PD-1 and 55% had TII that expressed PD-L1. Tum-B7-H3% was significantly higher (median 60 vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, including when factoring in cause of immunosuppression. No significant difference in Tum-PD-L1%, TII-PD-L1%, CD8 density, or CD8-PD-1% was observed. Tumors from HIV+ patients lacked PD-L1 expression, and had lower B7-H3% (median 2.5 vs. 60%, p = 0.007), and higher CD8 density (median 75% vs. 40%, p = 0.04) compared to immunocompetent patients. Higher tumor grade (R = 0.34, p = 0.006) and LVI (R = 0.61, p < 0.001) were both associated with higher Tum-PD-L1%.
CONCLUSION
cSCC showed expression of PD-L1 on tumor in 26% of cases, and high tumor B7-H3 expression (85%) and PD-1 expression on CD8 TILs (80%). Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.
背景
通过免疫状态来描述皮肤鳞状细胞癌(cSCC)中协同信号分子 PD-L1、PD-1 和 B7-H3 的表达。
方法
我们回顾性分析了 2012 年至 2015 年期间接受手术切除的 66 例 cSCC 病例。对免疫染色的肿瘤切片进行分析，以确定 PD-L1（肿瘤 PD-L1%）、B7-H3（肿瘤 B7-H3%）、肿瘤周围和肿瘤内 CD8 T 细胞密度（CD8 密度）、表达 PD-1 的 CD8 T 细胞比例（CD8-PD-1%）和肿瘤浸润免疫细胞表达 PD-L1（TII-PD-L1%）的肿瘤细胞比例。
结果
在 66 例病例中，42 例为免疫功能正常，24 例为免疫抑制（13 例器官移植，8 例 HIV+，3 例其他）。将阳性表达定义为>5%，有 26%的肿瘤 PD-L1 阳性，85%的肿瘤 B7-H3 阳性，80%的 CD8 T 细胞表达 PD-1，55%的肿瘤浸润免疫细胞表达 PD-L1。免疫功能正常组的肿瘤 B7-H3%明显高于免疫抑制组（中位数 60%比 28%，p=0.025），包括免疫抑制的原因。肿瘤 PD-L1%、TII-PD-L1%、CD8 密度或 CD8-PD-1%无显著差异。HIV+患者的肿瘤缺乏 PD-L1 表达，B7-H3%较低（中位数 2.5%比 60%，p=0.007），CD8 密度较高（中位数 75%比 40%，p=0.04）。肿瘤分级较高（R=0.34，p=0.006）和脉管侵犯（R=0.61，p<0.001）均与较高的肿瘤 PD-L1%相关。
结论
cSCC 有 26%的病例在肿瘤上表达 PD-L1，85%的病例表达高肿瘤 B7-H3 和 80%的 CD8 TILs 表达 PD-1。在免疫功能正常的患者中，肿瘤 B7-H3 的表达明显高于免疫抑制的患者，这主要是由于 HIV+患者的表达非常低。
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