Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment

• Published in: Cell metabolism Vol. 33; no. 6; pp. 1205 - 1220.e5
• Main Authors: Poznanski, Sophie M., Singh, Kanwaldeep, Ritchie, Tyrah M., Aguiar, Jennifer A., Fan, Isabella Y., Portillo, Ana L., Rojas, Eduardo A., Vahedi, Fatemeh, El-Sayes, Abdullah, Xing, Sansi, Butcher, Martin, Lu, Yu, Doxey, Andrew C., Schertzer, Jonathan D., Hirte, Hal W., Ashkar, Ali A.
• Format: Journal Article
• Language: English
• Published: United States 01.06.2021
• Subjects: Adult; Aged; Animals; Antineoplastic Agents - immunology; Cell Line, Tumor; Female; Humans; Immunotherapy - methods; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Male; Mice; Middle Aged; Neoplasms - therapy; Tumor Microenvironment; Young Adult; NK cells; metabolic flexibility; immunometabolism; cancer immunotherapy; NK cell metabolism; tumor microenvironment; adoptive cell therapy; glucose metabolism; oxidative stress; Warburg effect

NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we...