一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD47 和 SIRPα 巨噬细胞免疫检查点通路在非小细胞肺癌中的表达
英文原题：Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer.
查看英文原题
Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer.
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研究概要
TAM 在可手术 NSCLC 的预后中发挥重要作用。
中文摘要
背景
癌细胞通过表达CD47整合素相关蛋白逃避巨噬细胞吞噬；CD47可与巨噬细胞表达的信号调节蛋白α（SIRPα）配体结合。针对这一通路的免疫治疗正在临床开发中。
方法
在98例非小细胞肺癌（NSCLC）病例中，研究CD47／SIRP分子表达，同时评估肿瘤间质中的CD68阳性巨噬细胞、TIL（肿瘤浸润淋巴细胞）及PD-L1／PD-1分子。
结果
98例中有29例癌细胞呈广泛的膜性CD47表达。肿瘤相关巨噬细胞（TAM）不同程度表达SIRP和CD68。肿瘤内部区域CD68巨噬细胞评分较高与总生存期改善相关（p=0.005），且该关系独立于分期（p=0.02，风险比0.4）。相反，CD68阳性TAM的SIRP表达较高（SIRP／CD68比值较高）与癌细胞CD47表达、TIL评分较低及较差预后相关（p=0.02）。此外，癌细胞CD47表达与FOXP3阳性TIL百分比呈直接相关（p=0.01，r=0.25）。
结论
TAM对可手术NSCLC患者预后具有重要影响。由于SIRP阳性巨噬细胞与不良预后相关，CD47／SIRP轴可作为辅助免疫治疗的合理靶点，以提高可手术NSCLC患者的治愈率。
展开英文摘要原文
BACKGROUND
Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRP ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development.
METHODS
We investigated the expression of CD47/SIRP molecules in a series of 98 NSCLCs, in parallel with the infiltration of tumor stroma by CD68+ macrophages, tumor-infiltrating lymphocytes (TILs), and PD-L1/PD-1 molecules.
RESULTS
Extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRP and CD68 were expressed, to a varying extent, by tumor-associated macrophages ( , TAMs). A high CD68M -score in inner tumor areas was linked with improved overall survival ( p = 0.005); and this was independent of the stage ( p = 0.02, hazard ratio 0.4). In contrast, high SIRP expression by CD68+ TAMs (SIRP /CD68-ratio) was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis ( p = 0.02). A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs ( p = 0.01, r = 0.25) was also noted.
CONCLUSIONS
TAMs play an important role in the prognosis of operable NSCLC. As SIRP + macrophages adversely affect prognosis, it is suggested that the CD47/SIRP axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC.
论文信息
- 作者
- Giatromanolaki A、Mitrakas A、Anestopoulos I、Kontosis A、Koukourakis IM、Pappa A、Panayiotidis MI、Koukourakis MI
- 第一作者单位
- Department of Pathology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.Greece
- 通讯作者单位
- Department of Radiotherapy/Oncology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.Greece
- 期刊
- Cancers2022 Apr 1
- 原文标识
- PubMed 35406573 · DOI 10.3390/cancers14071801
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