| First Author | Ni J | Year | 2020 |
| Journal | Immunity | Volume | 52 |
| Issue | 6 | Pages | 1075-1087.e8 |
| PubMed ID | 32445619 | Mgi Jnum | J:317448 |
| Mgi Id | MGI:6706581 | Doi | 10.1016/j.immuni.2020.05.001 |
| Citation | Ni J, et al. (2020) Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1alpha Unleashes NK Cell Activity. Immunity 52(6):1075-1087.e8 |
| abstractText | Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcription factor HIF-1alpha. Here, we defined the transcriptional landscape of mouse tumor-infiltrating natural killer (NK) cells by using single-cell RNA sequencing. Conditional deletion of Hif1a in NK cells resulted in reduced tumor growth, elevated expression of activation markers, effector molecules, and an enriched NF-kappaB pathway in tumor-infiltrating NK cells. Interleukin-18 (IL-18) from myeloid cells was required for NF-kappaB activation and the enhanced anti-tumor activity of Hif1a(-/-) NK cells. Extended culture with an HIF-1alpha inhibitor increased human NK cell responses. Low HIF1A expression was associated with high expression of IFNG in human tumor-infiltrating NK cells, and an enriched NK-IL18-IFNG signature in solid tumors correlated with increased overall patient survival. Thus, inhibition of HIF-1alpha unleashes NK cell anti-tumor activity and could be exploited for cancer therapy. |
