PD-1 + regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer

Significance PD-1 blockade is a cancer immunotherapy effective in various types of cancer. However, we observed rapid cancer progression, called hyperprogressive disease (HPD), in ∼10% of advanced gastric cancer patients treated with anti–PD-1 monoclonal antibody. Tumors of HPD patients possessed highly proliferating FoxP3 + Treg cells after treatment, contrasting with their reduction in non-HPD tumors. In vitro PD-1 blockade augmented proliferation and suppressive activity of human Treg cells. Likewise, murine Treg cells that were deficient in PD-1 signaling were more proliferative and immunosuppressive. Thus, HPD may occur when PD-1 blockade activates and expands tumor-infiltrating PD-1 + Treg cells to…

• NF
  Naito Foundation
• JA
  Japan Agency for Medical Research and Development

  Awards: 16cm0106301h0002, 17gm0410016h0006, 18gm0010005h0001, 18cm0106340h0001, 18cm0106303h0003
• MO
  Ministry of Education, Culture, Sports, Science and Technology

  Awards: 16K15551, 18J21161, 17K18388, 17H06162, 17J09900, 16H06295
• TM
  Takeda Medical Research Foundation
• KF
  Kobayashi Foundation for Cancer Research
• OP
  Ono Pharmaceutical