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@ARTICLE{Liu:289225,
author = {C. Liu and J. Xie and B. Lin and W. Tian and Y. Wu and S.
Xin and L. Hong and X. Li$^*$ and L. Liu and Y. Jin and H.
Tang and X. Deng and Y. Zou and S. Zheng and W. Fang and J.
Cheng and X. Dai and X. Bao and P. Zhao},
title = {{P}an-{C}ancer {S}ingle-{C}ell and {S}patial-{R}esolved
{P}rofiling {R}eveals the {I}mmunosuppressive {R}ole of
{APOE}+ {M}acrophages in {I}mmune {C}heckpoint {I}nhibitor
{T}herapy.},
journal = {Advanced science},
volume = {11},
number = {23},
issn = {2198-3844},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2024-00659},
pages = {e2401061},
year = {2024},
note = {2024 Jun;11(23):e2401061},
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.},
keywords = {APOE+ macrophages (Other) / immune checkpoint inhibitor
(Other) / machine learning algorithm (Other) / pan‐cancer
(Other) / single‐cell RNA sequencing (Other)},
cin = {F180 / D440},
ddc = {624},
cid = {I:(DE-He78)F180-20160331 / I:(DE-He78)D440-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38569519},
doi = {10.1002/advs.202401061},
url = {https://inrepo02.dkfz.de/record/289225},
}