Details

Autor(en) / Beteiligte

• Kim, Myeong Joon
• Kim, Kyungsoo
• Park, Hyo Jin
• Kim, Gil-Ran
• Hong, Kyeong Hee
• Oh, Ji Hoon
• Son, Jimin
• Park, Dong Jin
• Kim, Dahae
• Choi, Je-Min
• Lee, Insuk
• Ha, Sang-Jun

Titel

Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells

Ist Teil von

• Nature immunology, 2023-01, Vol.24 (1), p.148-161

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Regulatory T (T ) cells have an immunosuppressive function and highly express the immune checkpoint receptor PD-1 in the tumor microenvironment; however, the function of PD-1 in tumor-infiltrating (TI) T cells remains controversial. Here, we showed that conditional deletion of PD-1 in T cells delayed tumor progression. In Pdcd1 Foxp3 mice, in which both PD-1-expressing and PD-1-deficient T cells coexisted in the same tissue environment, conditional deletion of PD-1 in T cells resulted in impairment of the proliferative and suppressive capacity of TI T cells. PD-1 antibody therapy reduced the TI T cell numbers, but did not directly restore the cytokine production of TI CD8 T cells in TC-1 lung cancer. Single-cell analysis indicated that PD-1 signaling promoted lipid metabolism, proliferation and suppressive pathways in TI T cells. These results suggest that PD-1 ablation or inhibition can enhance antitumor immunity by weakening T cell lineage stability and metabolic fitness in the tumor microenvironment.