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GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.

Publication ,  Journal Article
Ancey, P-B; Contat, C; Boivin, G; Sabatino, S; Pascual, J; Zangger, N; Perentes, JY; Peters, S; Abel, ED; Kirsch, DG; Rathmell, JC; Meylan, E ...
Published in: Cancer Res
May 1, 2021

Neutrophils are the most abundant circulating leucocytes and are essential for innate immunity. In cancer, pro- or antitumor properties have been attributed to tumor-associated neutrophils (TAN). Here, focusing on TAN accumulation within lung tumors, we identify GLUT1 as an essential glucose transporter for their tumor supportive behavior. Compared with normal neutrophils, GLUT1 and glucose metabolism increased in TANs from a mouse model of lung adenocarcinoma. To elucidate the impact of glucose uptake on TANs, we used a strategy with two recombinases, dissociating tumor initiation from neutrophil-specific Glut1 deletion. Loss of GLUT1 accelerated neutrophil turnover in tumors and reduced a subset of TANs expressing SiglecF. In the absence of GLUT1 expression by TANs, tumor growth was diminished and the efficacy of radiotherapy was augmented. Our results demonstrate the importance of GLUT1 in TANs, which may affect their pro- versus antitumor behavior. These results also suggest targeting metabolic vulnerabilities to favor antitumor neutrophils. SIGNIFICANCE: Lung tumor support and radiotherapy resistance depend on GLUT1-mediated glucose uptake in tumor-associated neutrophils, indicating that metabolic vulnerabilities should be considered to target both tumor cells as well as innate immune cells. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/9/2345/F1.large.jpg.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

May 1, 2021

Volume

81

Issue

9

Start / End Page

2345 / 2357

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Treatment Failure
  • Oncology & Carcinogenesis
  • Neutrophils
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lung Neoplasms
  • Humans
  • Glucose Transporter Type 1
 

Citation

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Ancey, P.-B., Contat, C., Boivin, G., Sabatino, S., Pascual, J., Zangger, N., … Meylan, E. (2021). GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy. Cancer Res, 81(9), 2345–2357. https://doi.org/10.1158/0008-5472.CAN-20-2870
Ancey, Pierre-Benoit, Caroline Contat, Gael Boivin, Silvia Sabatino, Justine Pascual, Nadine Zangger, Jean Yannis Perentes, et al. “GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.Cancer Res 81, no. 9 (May 1, 2021): 2345–57. https://doi.org/10.1158/0008-5472.CAN-20-2870.
Ancey P-B, Contat C, Boivin G, Sabatino S, Pascual J, Zangger N, et al. GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy. Cancer Res. 2021 May 1;81(9):2345–57.
Ancey, Pierre-Benoit, et al. “GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.Cancer Res, vol. 81, no. 9, May 2021, pp. 2345–57. Pubmed, doi:10.1158/0008-5472.CAN-20-2870.
Ancey P-B, Contat C, Boivin G, Sabatino S, Pascual J, Zangger N, Perentes JY, Peters S, Abel ED, Kirsch DG, Rathmell JC, Vozenin M-C, Meylan E. GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy. Cancer Res. 2021 May 1;81(9):2345–2357.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

May 1, 2021

Volume

81

Issue

9

Start / End Page

2345 / 2357

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Treatment Failure
  • Oncology & Carcinogenesis
  • Neutrophils
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lung Neoplasms
  • Humans
  • Glucose Transporter Type 1