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免疫基因组分析黑色素瘤肿瘤浸润免疫细胞与总生存期的相关性。

Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis.

机构信息

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Tongji University Cancer Center, Shanghai, China.

出版信息

Cancer Med. 2020 Nov;9(22):8444-8456. doi: 10.1002/cam4.3466. Epub 2020 Sep 15.

DOI:10.1002/cam4.3466
PMID:32931642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7666744/
Abstract

AIMS

Different types of tumor-infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor-infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies.

METHODS

We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment.

RESULTS

In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8 T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell-related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF-β pathways were identified as participants of the crosstalk in CD8 T cells, Tregs, and M2 macrophages in the melanoma microenvironment.

CONCLUSION

These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma.

摘要

目的

不同类型的肿瘤浸润免疫细胞不仅增强，而且抑制黑色素瘤微环境中的抗肿瘤免疫。因此，全面了解黑色素瘤中的肿瘤浸润免疫细胞，并探索免疫治疗的新策略至关重要。

方法

我们通过免疫、基质和恶性肿瘤组织中基质和免疫细胞估计表达数据（ESTIMATE）评分分析了不同阶段黑色素瘤患者的免疫状态。使用估计相对 RNA 转录物子集（CIBERSORTx）算法在 471 个黑色素瘤和 324 个健康组织中鉴定免疫细胞类型。此外，我们进行了基因集变异分析（GSVA）以确定肿瘤微环境中差异调节的途径。

结果

在黑色素瘤队列中，我们发现 ESTIMATE 和免疫评分与生存或肿瘤临床阶段有关。在 22 种免疫细胞中，CIBERSORTx 算法显示 CD8 T 细胞、M2 巨噬细胞和调节性 T 细胞（Tregs）有显著差异。此外，GSVA 确定了与免疫细胞相关的途径；原发性免疫缺陷途径、肠免疫网络 IgA 和 TGF-β 途径被确定为黑色素瘤微环境中 CD8 T 细胞、Tregs 和 M2 巨噬细胞相互作用的参与者。

结论

这些结果揭示了黑色素瘤中免疫细胞的细胞和分子特征，为选择免疫治疗的靶点和提高治疗黑色素瘤的疗效提供了一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/cd6045973d36/CAM4-9-8444-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/67a78196f6d9/CAM4-9-8444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/89ae3856c47a/CAM4-9-8444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/161fc9e6346d/CAM4-9-8444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/7d7d9f03b092/CAM4-9-8444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/8054bd62eb34/CAM4-9-8444-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/cd6045973d36/CAM4-9-8444-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/67a78196f6d9/CAM4-9-8444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/89ae3856c47a/CAM4-9-8444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/161fc9e6346d/CAM4-9-8444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/7d7d9f03b092/CAM4-9-8444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/8054bd62eb34/CAM4-9-8444-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f2/7666744/cd6045973d36/CAM4-9-8444-g006.jpg

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