Details

Autor(en) / Beteiligte

• Neo, Shi Yong
• Yang, Ying
• Record, Julien
• Ma, Ran
• Chen, Xinsong
• Chen, Ziqing
• Tobin, Nicholas P
• Blake, Emily
• Seitz, Christina
• Thomas, Ron
• Wagner, Arnika Kathleen
• Andersson, John
• de Boniface, Jana
• Bergh, Jonas
• Murray, Shannon
• Alici, Evren
• Childs, Richard
• Johansson, Martin
• Westerberg, Lisa S
• Haglund, Felix
• Hartman, Johan
• Lundqvist, Andreas

Titel

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

Ist Teil von

• The Journal of clinical investigation, 2020-03, Vol.130 (3), p.1185-1198

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.