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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.