Journal Article

DKFZ-2024-00659

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Pan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.

Liu, C. ; Xie, J. ; Lin, B. ; Tian, W. ; Wu, Y. ; Xin, S. ; Hong, L. ; Li, X.DKFZ* ; Liu, L. ; Jin, Y. ; Tang, H. ; Deng, X. ; Zou, Y. ; Zheng, S. ; Fang, W. ; Cheng, J. ; Dai, X. ; Bao, X. ; Zhao, P.

2024
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/advs.202401061

Abstract: The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single-cell RNA sequencing (scRNA-seq) and machine learning methods. The scRNA-seq and bulk RNA-seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single-cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan-cancer patients. The proportion of APOE+ macrophages is higher in ICI non-responders of triple-negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor-bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real-world immunotherapy data accurately predicts the ICI response of pan-cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells.

Keyword(s): APOE+ macrophages ; immune checkpoint inhibitor ; machine learning algorithm ; pan‐cancer ; single‐cell RNA sequencing

Note: 2024 Jun;11(23):e2401061

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Contributing Institute(s):

1. Chronische Entzündung und Krebs (F180)
2. Chronische Entzündung und Krebs (D440)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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