间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题，原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
胃癌分子亚型中肿瘤细胞与免疫细胞的空间分布及其与 PD-L1 的相关性
英文原题：Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers.
查看英文原题
Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers.
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中文摘要
(1) 背景：EBV 阳性和错配修复缺陷（MMRd）胃癌（GC）表现出更高水平的 TIL 和 PD-L1 表达，因此对免疫治疗有更显著的反应。
然而，大多数 GC 为 EBV 阴性（EBV-）且 MMR proficient（MMRp）。我们分析了 EBV-MMRpGC 中的 PD-L1 表达和 TIL，并与 EBV 阳性（EBV+）和 MMRdGC 进行比较，以识别对免疫治疗敏感的免疫原性表型。(2) 方法：对 409 例原发性切除 GC 的新一代组织芯片通过 Epstein-Barr 编码区（EBER）原位杂交检测 MSH1、PMS2、MSH2、MSH6、PD-L1 和 CD8 免疫组化进行分析。PD-L1 阳性定义为联合阳性评分（CPS）≥1。CD8+ TIL 及其与癌细胞的邻近程度在 HALO 图像分析平台上进行数字化分析。(3) 结果：11 例为 EBV+，49 例为 MMRd，349 例为 EBV-MMRpGC。
PD-L1 阳性率最高见于 EBV+GC，其次为 MMRdGC 和 EBV-MMRpGC（分别为 81.8%、73.5% 和 27.8%）。与 EBV-MMRpGC 相比，EBV+ 和 MMRdGC 还表现出 CD8+ TIL 数量增加及其与肿瘤细胞的邻近程度增加（每项 p < 0.001）。PD-L1 状态与所有亚型中 CD8+ TIL 总数及其与肿瘤细胞的邻近程度呈正相关，包括 EBV-MMRpGC（每项 p < 0.001）。共有 28.4% 的 EBV-MMRpGC 显示高 CD8+ TIL，且不依赖于 PD-L1。(4) 结论：PD-L1 和 CD8 免疫组化，辅以数字图像分析，可能识别具有高免疫反应指数的 EBV-MMRpGC，提示对免疫治疗敏感。
展开英文摘要原文
(1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy.
However, the majority of GCs are EBV-negative (EBV ) and MMR proficient (MMRp).
We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of 1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs.
The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81. 8%, 73. 5%, and 27. 8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (p < 0. 001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (p < 0.
001 each). A total of 28. 4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy.
论文信息
- 作者
- Dislich B、Mertz KD、Gloor B、Langer R
- 第一作者单位
- Institute of Pathology, University of Bern, 3008 Bern, Switzerland.Switzerland
- 通讯作者单位
- Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University, 4021 Linz, Austria.Austria
- 期刊
- Cancers2022 Mar 29
- 原文标识
- PubMed 35406506 · DOI 10.3390/cancers14071736
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