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Hui, B.* ; Lu, C.* ; Li, H.* ; Hao, X.* ; Liu, H.* ; Zhuo, D.* ; Wang, Q. ; Li, Z.* ; Liu, L.* ; Wang, X.* ; Gu, Y.* ; Tang, W.*

Inhibition of APOE potentiates immune checkpoint therapy for cancer.

Int. J. Biol. Sci. 18, 5230-5240 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Checkpoint immunotherapy is capable of unleashing T cells for controlling tumor, whereas it is destroyed by immunosuppressive myeloid cell. Apoprotein E (APOE) refers to a ligand in terms of the members of low-density lipoprotein (LDL) receptor family for mediating Apoprotein B-involving atherogenic lipoprotein clearance. Besides, tumor-infiltration macrophage can express APOE. The present study reported Apoe-/- mice to exhibit higher resistance toward the development of three types of carcinomas as compared with mice with wild type and to have greater responses to αPD-1 (anti-PD-1) immunotherapy. Moreover, treatment by exploiting APOE inhibitor (COG 133TFA, αAPOE) was capable of curbing tumor development and fostering regression if in combination of αPD-1. According to single-cell RNA sequencing (scRNA-seq), Apoe deletion was correlated with the decline of C1QC+ and CCR2+ macrophage within tumor infiltration, and mass spectrometry results noticeably showed down-regulated the number of M2 macrophages as well. Furthermore, APOE expression in cancer patients resistant to αPD-1 treatment significantly exceeded that in the sensitive group. For this reason, APOE is likely to be targeted for modifying tumor macrophage infiltrate and augmenting checkpoint immunotherapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apoe ; Macrophage ; Pd-1 ; Single-cell Rna Sequencing ; Tigit
ISSN (print) / ISBN 1449-2288
e-ISSN 1449-2288
Zeitschrift International Journal of Biological Sciences
Quellenangaben Band: 18, Heft: 14, Seiten: 5230-5240 Artikelnummer: , Supplement: ,
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Förderungen China Scholarship Council
National Natural Science Foundation of China