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肿瘤和癌症免疫治疗研究中的免疫受体库的全面特征分析。

Comprehensive Characterizations of Immune Receptor Repertoire in Tumors and Cancer Immunotherapy Studies.

机构信息

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.

Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

出版信息

Cancer Immunol Res. 2022 Jul 1;10(7):788-799. doi: 10.1158/2326-6066.CIR-21-0965.

DOI:10.1158/2326-6066.CIR-21-0965
PMID:35605261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9299271/
Abstract

We applied our computational algorithm TRUST4 to assemble immune receptor (T-cell receptor/B-cell receptor) repertoires from approximately 12,000 RNA sequencing samples from The Cancer Genome Atlas and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 sequences, we observed that the expression of CCL5 and MZB1 is the most positively correlated genes with T-cell clonal expansion and B-cell clonal expansion, respectively. We analyzed amino acid evolution during B-cell receptor somatic hypermutation and identified tyrosine as the preferred residue. We found that IgG1+IgG3 antibodies together with FcRn were associated with complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity or phagocytosis. In addition to B-cell infiltration, we discovered that B-cell clonal expansion and IgG1+IgG3 antibodies are also correlated with better patient outcomes. Finally, we created a website, VisualizIRR, for users to interactively explore and visualize the immune repertoires in this study. See related Spotlight by Liu and Han, p. 786.

摘要

我们应用计算算法 TRUST4 从癌症基因组图谱和七项免疫疗法研究的大约 12000 个 RNA 测序样本中组装免疫受体（T 细胞受体/B 细胞受体）库。从超过 3500 万个组装的完整互补决定区 3 序列中，我们观察到 CCL5 和 MZB1 的表达分别与 T 细胞克隆扩增和 B 细胞克隆扩增最正相关。我们分析了 B 细胞受体体细胞超突变过程中的氨基酸进化，并确定酪氨酸是首选残基。我们发现 IgG1+IgG3 抗体与 FcRn 一起与补体依赖性细胞毒性和抗体依赖性细胞毒性或吞噬作用相关。除了 B 细胞浸润外，我们还发现 B 细胞克隆扩增和 IgG1+IgG3 抗体也与更好的患者预后相关。最后，我们创建了一个网站 VisualizIRR，供用户交互探索和可视化本研究中的免疫库。见相关的刘和韩的 Spotlight，第 786 页。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/4949c3b99f79/nihms-1811915-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/b6c9e498bdaa/nihms-1811915-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/da0f2389cdac/nihms-1811915-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/f40efb5ab07f/nihms-1811915-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/e40df211436f/nihms-1811915-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/7436afd66c0f/nihms-1811915-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/4949c3b99f79/nihms-1811915-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/b6c9e498bdaa/nihms-1811915-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/da0f2389cdac/nihms-1811915-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/f40efb5ab07f/nihms-1811915-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/e40df211436f/nihms-1811915-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/7436afd66c0f/nihms-1811915-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ef/9299271/4949c3b99f79/nihms-1811915-f0006.jpg

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Nat Methods. 2021 Jun;18(6):627-630. doi: 10.1038/s41592-021-01142-2. Epub 2021 May 13.
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bioRxiv. 2024 Jul 22:2024.07.18.604205. doi: 10.1101/2024.07.18.604205.
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Front Immunol. 2024 Mar 27;15:1380641. doi: 10.3389/fimmu.2024.1380641. eCollection 2024.
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