RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
结肠癌中程序性死亡配体 1 (PD-L1) 及其与作为肿瘤-宿主拮抗物的肿瘤出芽和 TIL（肿瘤浸润淋巴细胞）(TILs) 的相互作用
英文原题：Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists.
查看英文原题
Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists.
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研究概要
PD-L1 阳性与良好预后标志物相关。
中文摘要
目的
分析结肠癌（CC）肿瘤微环境中程序性死亡配体 1（PD-L1）免疫组化的作用，重点关注肿瘤芽生与TIL（肿瘤浸润淋巴细胞）的相互关系，并阐明其对免疫肿瘤治疗决策的潜在价值。
方法
纳入 347 例 I 至 IV 期 CC 患者。使用两种抗体进行 PD-L1 免疫组化检测（22C3 pharmDx，Agilent；QR1，Quartett），评估肿瘤比例评分（TPS）和免疫细胞评分（IC）。依据国际肿瘤芽生共识会议（ITBCC）和国际 TIL 工作组（ITWG）标准评估肿瘤芽生及 TIL，并进行相关性和生存分析。
结果
PD-L1 阳性与 TIL>5% 及错配修复缺陷显著相关；使用两种抗体时，整体 PD-L1 阳性和 IC 阳性病例的总生存期（OS）均显著更长。“高级别”“右侧肿瘤”及“不论错配修复状态的 TIL>5%”可作为额外免疫治疗决策的潜在指标。此外，TPS 阳性与低肿瘤芽生相关。在 TIL 高表达组中，PD-L1 阳性病例更多。低芽生/高 TIL 组中，PD-L1 阳性病例无病生存期和 OS 更长。
结论
总体而言，PD-L1 阳性与良好预后标志物相关。PD-L1 免疫组化可识别可能用于免疫治疗的额外候选指标，也能在低芽生/高 TIL 组内对患者进行分层，并具有显著预后意义。
展开英文摘要原文
PURPOSE
To analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions.
METHODS
Three hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed.
RESULTS
PD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters "high grade," "right-sidedness," and "TILS > 5% regardless of MMR status" evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases.
CONCLUSION
Overall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.
论文信息
- 作者
- Lang-Schwarz C、Melcher B、Hartmann A、Bertz S、Dregelies T、Lang-Schwarz K、Vieth M、Sterlacci W
- 单位
- Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Str. 101, 95445, Bayreuth, Germany. Corinna.Lang-Schwarz@klinikum-bayreuth.de.Germany
- 期刊
- International journal of colorectal disease2021 Nov
- 原文标识
- PubMed 34170390 · DOI 10.1007/s00384-021-03985-9
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