Browse

Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis

Cited 45 time in Web of Science Cited 46 time in Scopus
Authors
Jeong, Hoibin; Kim, Sehui; Hong, Beom-Ju; Lee, Chan-Ju; Kim, Young-Eun; Bok, Seoyeon; Oh, Jung-Min; Gwak, Seung-Hee; Yoo, Min Young; Lee, Min Sun; Chung, Seock-Jin; Defrene, Joan; Tessier, Philippe; Pelletier, Martin; Jeon, Hyeongrin; Roh, Tae-Young; Kim, Bumju; Kim, Ki Hean; Ju, Ji Hyeon; Kim, Sungjee; Lee, Yoon-Jin; Kim, Dong-Wan; Kim, Il Han; Kim, Hak Jae; Park, Jong-Wan; Lee, Yun-Sang; Lee, Jae Sung; Cheon, Gi Jeong; Weissman, Irving L.; Chung, Doo Hyun; Jeon, Yoon Kyung; Ahn, G-One
Issue Date
2019-02
Citation
Cancer Research, Vol.79 No.4, pp.795-806
Abstract
Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here, we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in patients with non-small cell lung cancer (NSCLC). We found a strong correlation between CD68 TAM immunostaining and PET 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of patients with NSCLC. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 patients with NSCLC from The Cancer Genome Atlas database. TAM secreted TNF alpha to promote tumor cell glycolysis, whereas increased AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T-cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies, which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies, including immunotherapy. Significance: These findings show that tumor-associated macrophages can significantly modulate tumor metabolism, hindering the efficacy of anticancer therapies, including anti PD-L1 immunotherapy.
ISSN
0008-5472
URI
http://hdl.handle.net/10371/165217
DOI
https://doi.org/10.1158/0008-5472.CAN-18-2545
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse