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

ABSTRACT: PD-1 blockade is a cancer immunotherapy effective in various types of cancer. In a fraction of treated patients, however, it causes rapid cancer progression called hyperprogressive disease (HPD). With our observation of HPD in ∼10% of anti-PD-1 monoclonal antibody (mAb)-treated advanced gastric cancer (GC) patients, we explored how anti-PD-1 mAb caused HPD in these patients and how HPD could be treated and prevented. In the majority of GC patients, tumor-infiltrating FoxP3^highCD45RA^-CD4⁺ T cells [effector Treg (eTreg) cells], which were abundant and highly suppressive in tumors, expressed PD-1 at equivalent levels as tumor-infiltrating CD4⁺ or CD8⁺ effector/memory T cells and at much higher levels than circulating eTreg cells. Comparis

SUBMITTER: Kamada T 

PROVIDER: S-EPMC6525547 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature