Rongrong Wu, Yoshiya Horimoto, Masanori Oshi, Matthew G K Benesch, Thaer Khoury, Kazuaki Takabe, Takashi Ishikawa
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引用次数: 0
摘要
肿瘤浸润淋巴细胞是浸润肿瘤微环境的淋巴细胞或免疫细胞的总称。大量研究表明,肿瘤浸润淋巴细胞是乳腺癌强有力的预后和预测生物标志物。最近,直接针对肿瘤浸润淋巴细胞的免疫检查点抑制剂已成为三阴性乳腺癌标准治疗的一部分。令人惊讶的是,用传统方法量化的肿瘤浸润淋巴细胞并不能预测对免疫检查点抑制剂的反应,这凸显了肿瘤浸润淋巴细胞的异质性和肿瘤微环境中免疫网络的复杂性。肿瘤浸润淋巴细胞由多种免疫细胞群组成,包括细胞毒性 CD8 阳性 T 淋巴细胞、B 细胞和髓样细胞。传统上,肿瘤基质中的肿瘤浸润淋巴细胞通过组织学方法进行评估。然而,这种方法的标准化程度有限,因此需要使用各种新型技术来阐明肿瘤微环境的异质性。这篇综述概述了肿瘤浸润淋巴细胞的评估方法,从评估瘤内和基质肿瘤浸润淋巴细胞的传统病理方法(如免疫组化),到最近利用人工智能进行计算机组织成像、流式细胞仪分选和多组学分析的进步,这些方法利用高通量检测,使用免疫特征或解卷工具从大块肿瘤中估计肿瘤浸润淋巴细胞。我们还讨论了能够分析肿瘤浸润淋巴细胞异质性的更高分辨率技术,如单细胞分析和空间转录组学。随着个性化医疗时代的到来,临床医生了解这些技术非常重要。
Emerging measurements for tumor-infiltrating lymphocytes in breast cancer.
Tumor-infiltrating lymphocytes are a general term for lymphocytes or immune cells infiltrating the tumor microenvironment. Numerous studies have demonstrated tumor-infiltrating lymphocytes to be robust prognostic and predictive biomarkers in breast cancer. Recently, immune checkpoint inhibitors, which directly target tumor-infiltrating lymphocytes, have become part of standard of care treatment for triple-negative breast cancer. Surprisingly, tumor-infiltrating lymphocytes quantified by conventional methods do not predict response to immune checkpoint inhibitors, which highlights the heterogeneity of tumor-infiltrating lymphocytes and the complexity of the immune network in the tumor microenvironment. Tumor-infiltrating lymphocytes are composed of diverse immune cell populations, including cytotoxic CD8-positive T lymphocytes, B cells and myeloid cells. Traditionally, tumor-infiltrating lymphocytes in tumor stroma have been evaluated by histology. However, the standardization of this approach is limited, necessitating the use of various novel technologies to elucidate the heterogeneity in the tumor microenvironment. This review outlines the evaluation methods for tumor-infiltrating lymphocytes from conventional pathological approaches that evaluate intratumoral and stromal tumor-infiltrating lymphocytes such as immunohistochemistry, to the more recent advancements in computer tissue imaging using artificial intelligence, flow cytometry sorting and multi-omics analyses using high-throughput assays to estimate tumor-infiltrating lymphocytes from bulk tumor using immune signatures or deconvolution tools. We also discuss higher resolution technologies that enable the analysis of tumor-infiltrating lymphocytes heterogeneity such as single-cell analysis and spatial transcriptomics. As we approach the era of personalized medicine, it is important for clinicians to understand these technologies.
期刊介绍:
Japanese Journal of Clinical Oncology is a multidisciplinary journal for clinical oncologists which strives to publish high quality manuscripts addressing medical oncology, clinical trials, radiology, surgery, basic research, and palliative care. The journal aims to contribute to the world"s scientific community with special attention to the area of clinical oncology and the Asian region.
JJCO publishes various articles types including:
・Original Articles
・Case Reports
・Clinical Trial Notes
・Cancer Genetics Reports
・Epidemiology Notes
・Technical Notes
・Short Communications
・Letters to the Editors
・Solicited Reviews