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000289225 1001_ $$aLiu, Chuan$$b0
000289225 245__ $$aPan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.
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000289225 520__ $$aThe 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.
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000289225 650_7 $$2Other$$aAPOE+ macrophages
000289225 650_7 $$2Other$$aimmune checkpoint inhibitor
000289225 650_7 $$2Other$$amachine learning algorithm
000289225 650_7 $$2Other$$apan‐cancer
000289225 650_7 $$2Other$$asingle‐cell RNA sequencing
000289225 7001_ $$aXie, Jindong$$b1
000289225 7001_ $$aLin, Bo$$b2
000289225 7001_ $$aTian, Weihong$$b3
000289225 7001_ $$aWu, Yifan$$b4
000289225 7001_ $$aXin, Shan$$b5
000289225 7001_ $$aHong, Libing$$b6
000289225 7001_ $$0P:(DE-He78)128e4949aa4cb04fe109c52df0c67732$$aLi, Xin$$b7$$udkfz
000289225 7001_ $$aLiu, Lulu$$b8
000289225 7001_ $$aJin, Yuzhi$$b9
000289225 7001_ $$aTang, Hailin$$b10
000289225 7001_ $$aDeng, Xinpei$$b11
000289225 7001_ $$00000-0002-5205-9923$$aZou, Yutian$$b12
000289225 7001_ $$aZheng, Shaoquan$$b13
000289225 7001_ $$aFang, Weijia$$b14
000289225 7001_ $$aCheng, Jinlin$$b15
000289225 7001_ $$aDai, Xiaomeng$$b16
000289225 7001_ $$00000-0002-6232-3783$$aBao, Xuanwen$$b17
000289225 7001_ $$aZhao, Peng$$b18
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