Details

Autor(en) / Beteiligte

• Lim, Jing Xuan
• Lai, Chester Y
• Mallett, Grace E
• McDonald, David
• Hulme, Gillian
• Laba, Stephanie
• Shapanis, Andrew
• Payne, Megan
• Patterson, Warren
• Alexander, Michael
• Coxhead, Jonathan
• Filby, Andrew
• Plummer, Ruth
• Lovat, Penny E
• Sciume, Giuseppe
• Healy, Eugene
• Amarnath, Shoba

Titel

Programmed cell death-1 receptor-mediated regulation of Tbet + NK1.1 - innate lymphoid cells within the tumor microenvironment

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2023-05, Vol.120 (18), p.e2216587120-e2216587120

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Innate lymphoid cells (ILCs) play a key role in tissue-mediated immunity and can be controlled by coreceptor signaling. Here, we define a subset of ILCs that are Tbet NK1.1 and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet NK1.1 ILCs. PD-1 significantly controlled the proliferation and function of Tbet NK1.1 ILCs in multiple murine and human tumors. We found tumor-derived lactate enhanced PD-1 expression on Tbet NK1.1 ILCs within the TME, which resulted in dampened the mammalian target of rapamycin (mTOR) signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1-deficient Tbet NK1.1 ILCs expressed significantly increased IFNγ and granzyme B and K. Furthermore, PD-1-deficient Tbet NK1.1 ILCs contributed toward diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate antitumor responses of Tbet NK1.1 ILCs within the TME.