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
英文原题:Fast TILs-A pipeline for efficient TILs estimation in non-small cell Lung cancer.
Fast TILs-A pipeline for efficient TILs estimation in non-small cell Lung cancer.
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TIL(肿瘤浸润淋巴细胞)在非小细胞肺癌(NSCLC)中的预后价值已得到充分证实。然而,在苏木精-伊红(H&E)全切片图像(WSI)中手工计数TIL既费时又容易产生差异。
本研究旨在开发并验证一套自动化计算流程,用于量化NSCLC全切片图像中的TIL。此类计算病理学工具可加速TIL评估,标准化预后判断并促进个体化治疗。
本研究开发了端到端自动化流程,将基于苏木精成分过滤的图像块提取方法,与基于机器学习的图像块分类及采用HoVer-Net架构的细胞定量方法相结合;另以随机抽样进一步减少处理的图像块数量。通过患者生存数据评估抽样效果、流程识别信息性图像块的能力、计算效率及评分的临床价值。该流程可选择性处理有信息量的图像块,在计算效率和预后判别能力之间取得平衡。过滤后约70%的候选图像块被排除;仅需处理符合条件图像块的5%,即可保持预后准确性(C指数=.65),且相较于分析全部过滤后图像块,整体计算时间相应线性减少。该流程的TIL评分与患者生存显著相关,且优于传统CD8免疫组化评分(C指数=.59);Kaplan-Meier分析进一步证实其预后价值。
本研究提出一种用于肺癌WSI中TIL评估的自动化流程,有望成为改善NSCLC个体化治疗的预后工具。其计算效率提升(尤其是处理时间的缩短)和临床相关性标志着计算病理学的进步。
The prognostic relevance of tumor-infiltrating lymphocytes (TILs) in non-small cell Lung cancer (NSCLC) is well-established.
However, manual TIL quantification in hematoxylin and eosin (H&E) whole slide images (WSIs) is laborious and prone to variability. To address this, we aim to develop and validate an automated computational pipeline for the quantification of TILs in WSIs of NSCLC. Such a solution in computational pathology can accelerate TIL evaluation, thereby standardizing the prognostication process and facilitating personalized treatment strategies.
We develop an end-to-end automated pipeline for TIL estimation in Lung cancer WSIs by integrating a patch extraction approach based on hematoxylin component filtering with a machine learning-based patch classification and cell quantification method using the HoVer-Net model architecture.
Additionally, we employ randomized patch sampling to further reduce the processed patch amount.
We evaluate the effectiveness of the patch sampling procedure, the pipeline's ability to identify informative patches and computational efficiency, and the clinical value of produced scores using patient survival data.
Our pipeline demonstrates the ability to selectively process informative patches, achieving a balance between computational efficiency and prognostic integrity. The pipeline filtering excludes approximately 70% of all patch candidates.
Further, only 5% of eligible patches are necessary to retain the pipeline's prognostic accuracy (c-index = 0. 65), resulting in a linear reduction of the total computational time compared to the filtered patch subset analysis. The pipeline's TILs score has a strong association with patient survival and outperforms traditional CD8 immunohistochemical scoring (c-index = 0. 59). Kaplan-Meier analysis further substantiates the TILs score's prognostic value.
This study introduces an automated pipeline for TIL evaluation in Lung cancer WSIs, providing a prognostic tool with potential to improve personalized treatment in NSCLC. The pipeline's computational advances, particularly in reducing processing time, and clinical relevance demonstrate a step forward in computational pathology.
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