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

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

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1 Citation (Scopus)


Regulatory T (Treg) 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) Treg cells remains controversial. Here, we showed that conditional deletion of PD-1 in Treg cells delayed tumor progression. In Pdcd1fl/flFoxp3eGFP−Cre-ERT2(+/−) mice, in which both PD-1-expressing and PD-1-deficient Treg cells coexisted in the same tissue environment, conditional deletion of PD-1 in Treg cells resulted in impairment of the proliferative and suppressive capacity of TI Treg cells. PD-1 antibody therapy reduced the TI Treg 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 Treg cells. These results suggest that PD-1 ablation or inhibition can enhance antitumor immunity by weakening Treg cell lineage stability and metabolic fitness in the tumor microenvironment.

Original languageEnglish
Pages (from-to)148-161
Number of pages14
JournalNature Immunology
Issue number1
Publication statusPublished - 2023 Jan

Bibliographical note

Funding Information:
This study was supported by National Research Foundation of Korea grants funded by the Korean government (2017R1A5A1014560, 2019M3A9B6065221 to S-.J.H.; 2018R1A5A2025079, 2019M3A9B6065192 to I.L.). This study was also supported by the Korean Health Technology R&D Project (HV20C0144, HN21C1410 to S-.J.H.) through the Korean Health Industry Development Institute funded by the Ministry of Health & Welfare. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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