TY  - JOUR
AU  - Liu, Chuan
AU  - Xie, Jindong
AU  - Lin, Bo
AU  - Tian, Weihong
AU  - Wu, Yifan
AU  - Xin, Shan
AU  - Hong, Libing
AU  - Li, Xin
AU  - Liu, Lulu
AU  - Jin, Yuzhi
AU  - Tang, Hailin
AU  - Deng, Xinpei
AU  - Zou, Yutian
AU  - Zheng, Shaoquan
AU  - Fang, Weijia
AU  - Cheng, Jinlin
AU  - Dai, Xiaomeng
AU  - Bao, Xuanwen
AU  - Zhao, Peng
TI  - Pan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.
JO  - Advanced science
VL  - 11
IS  - 23
SN  - 2198-3844
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2024-00659
SP  - e2401061
PY  - 2024
N1  - 2024 Jun;11(23):e2401061
AB  - 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.
KW  - APOE+ macrophages (Other)
KW  - immune checkpoint inhibitor (Other)
KW  - machine learning algorithm (Other)
KW  - pan‐cancer (Other)
KW  - single‐cell RNA sequencing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38569519
DO  - DOI:10.1002/advs.202401061
UR  - https://inrepo02.dkfz.de/record/289225
ER  -