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免疫功能表型分析对乳腺癌免疫循环功能障碍的影响

The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer.

作者信息

Takeshita Takashi, Torigoe Toshihiko, Yan Li, Huang Jing Li, Yamashita Hiroko, Takabe Kazuaki

机构信息

Department of Breast Surgery, Hokkaido University Hospital, Hokkaido 060-8648, Japan.

Department of Pathology, Sapporo Medical University School of Medicine, Hokkaido 060-8556, Japan.

出版信息

Cancers (Basel). 2020 Dec 31;13(1):110. doi: 10.3390/cancers13010110.

DOI:10.3390/cancers13010110
PMID:33396390
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7795596/
Abstract

The cancer-immunity cycle (CIC) is a series of self-sustaining stepwise events to fight cancer growth by the immune system. We hypothesized that immunofunctional phenotyping that represent the malfunction of the CIC is clinically relevant in breast cancer (BC). Total of 2979 BC cases; 1075 from TCGA cohort, 1904 from METABRIC cohort were analyzed. The immunofunctional phenotype was classified as follows: hot T-cell infiltrated (HTI), high immune cytolytic activity (CYT), Cold T-cell infiltrated (CTI), high frequency of CD8+ T cells and low CYT, and non-inflamed, low frequency of CD8+ T cells and low CYT. The analysis of tumor immune microenvironment in the immunofunctional phenotype revealed that not only immunostimulatory factors, but also immunosuppressive factors were significantly elevated and immunosuppressive cells were significantly decreased in HTI. Patients in HTI were significantly associated with better survival in whole cohort and patients in CTI were significantly associated with worse survival in triple negative. Furthers, HTI was inversely related to estrogen responsive signaling. We demonstrated that immunofunctional phenotype not only indicated the degree of anti-cancer immune dysfunction, but also served as a prognostic biomarker and HTI was inversely related to estrogen response.

摘要

癌症免疫循环（CIC）是免疫系统对抗癌症生长的一系列自我维持的逐步事件。我们假设，代表CIC功能失调的免疫功能表型在乳腺癌（BC）中具有临床相关性。共分析了2979例BC病例，其中1075例来自TCGA队列，1904例来自METABRIC队列。免疫功能表型分类如下：热T细胞浸润（HTI）、高免疫细胞溶解活性（CYT）、冷T细胞浸润（CTI）、CD8+T细胞高频率且CYT低，以及无炎症、CD8+T细胞低频率且CYT低。对免疫功能表型中的肿瘤免疫微环境分析显示，HTI中不仅免疫刺激因子显著升高，而且免疫抑制因子也显著升高，免疫抑制细胞显著减少。HTI患者在整个队列中的生存率显著更高，而CTI患者在三阴性乳腺癌中的生存率显著更低。此外，HTI与雌激素反应信号呈负相关。我们证明，免疫功能表型不仅表明抗癌免疫功能障碍的程度，还可作为一种预后生物标志物，且HTI与雌激素反应呈负相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/01ca0d64ab2f/cancers-13-00110-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/06d4954e8074/cancers-13-00110-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/5d3c816df5fa/cancers-13-00110-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/c9fe2d5176dd/cancers-13-00110-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/fd466fa06cc3/cancers-13-00110-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/01ca0d64ab2f/cancers-13-00110-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/06d4954e8074/cancers-13-00110-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/5d3c816df5fa/cancers-13-00110-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/c9fe2d5176dd/cancers-13-00110-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/fd466fa06cc3/cancers-13-00110-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f0c/7795596/01ca0d64ab2f/cancers-13-00110-g005.jpg

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Molecular Biological Features of Nottingham Histological Grade 3 Breast Cancers.诺丁汉组织学分级 3 级乳腺癌的分子生物学特征。
Ann Surg Oncol. 2020 Oct;27(11):4475-4485. doi: 10.1245/s10434-020-08608-1. Epub 2020 May 20.
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Immune Cytolytic Activity for Comprehensive Understanding of Immune Landscape in Hepatocellular Carcinoma.
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