First Author | Ancey PB | Year | 2021 |
Journal | Cancer Res | Volume | 81 |
Issue | 9 | Pages | 2345-2357 |
PubMed ID | 33753374 | Mgi Jnum | J:305534 |
Mgi Id | MGI:6706777 | Doi | 10.1158/0008-5472.CAN-20-2870 |
Citation | Ancey PB, et al. (2021) Glut1 expression in tumor-associated neutrophils promotes lung cancer growth and resistance to radiotherapy. Cancer Res 81(9):2345-2357 |
abstractText | Neutrophils are the most abundant circulating leucocytes and are essential for innate immunity. In cancer, pro- or anti-tumor 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 to 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 anti-tumor behavior. These results also suggest targeting metabolic vulnerabilities to favor anti-tumor neutrophils. |