Inhibition of APOE potentiates immune checkpoint therapy for cancer

Hui, Bingqing; Lu, Chen; Li, Haiyang; Hao, Xiaopei; Liu, Hanyuan; Zhuo, Danping; Wang, Qian; Li, Zhouxiao; Liu, Li; Wang, Xuehao; Gu, Yanhong und Tang, Weiwei (2022): Inhibition of APOE potentiates immune checkpoint therapy for cancer. In: International Journal of Biological Sciences, Bd. 18, Nr. 14: S. 5230-5240

Abstract

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 alpha PD-1 (anti-PD-1) immunotherapy. Moreover, treatment by exploiting APOE inhibitor (COG 133TFA, alpha APOE) was capable of curbing tumor development and fostering regression if in combination of alpha PD-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 alpha PD-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1449-2288
• Sprache: Englisch