Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

• DOI: 10.1073/pnas.1921445117
• Publication Date: 2020-03-12T00:15:38Z
• Authors: Xiaodong Wang; Xiaohui Yang; Chang Zhang; Yang Wang; Tianyou Cheng; Liqiang Duan; Zhou Tong; Shuguang Tan; Hangjie Zhang; Phei Er Saw; Yinmin Gu; Jinhua Wang; Yibi Zhang; Lina Shang; Yajuan Liu; Siyuan Jiang; Bingxue Yan; Rong Li; Yue Yang; Jie Yu; Yunzhao Chen; George Fu Gao; Qinong Ye; Shan Gao
• Keywords: Cancer Immunotherapy

Significance This study indicates that a subpopulation of tumor cells expresses both PD-1 and PD-L1, which decreases the growth by suppressing canonical signaling pathways, i.e. AKT ERK1/2 pathways. In absence adaptive immune system, cell-intrinsic PD-1/PD-L1 mediates resistance to treatment with FDA-approved anti-PD-1/PD-L1 antibodies activating ERK1/2. These findings provide an additional explanation for cancer immunotherapy.