Peng et al. investigated roles of dendritic cell (DC)-expressed PD-L1 on T cell activation and during PD-L1 blockade. In a DC-specific conditional PD-L1-/- mouse, MC38 tumors grew more slowly compared to in wild-type mice and did not respond to PD-L1 blockade, suggesting PD-L1 on DCs plays a key role in tumor antigen-specific T cell priming. IFNγ-induced upregulation of PD-L1 on DCs protected DCs from cytotoxic T cell killing, but, in established tumors, resulted in dampening TIL responses, which could be re-activated with anti-PD-L1. The study identified a dynamic and essential role for PD-L1 on DCs.
Contributed by Katherine Turner
ABSTRACT: Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.
Author Info: (1) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, 10
Author Info: (1) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, 100084, Beijing, China. (2) Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA. (3) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. (4) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. (5) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. (6) Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA. (7) Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. (8) Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. (9) Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA. (10) Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA. (11) School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China. hdtang@tsinghua.edu.cn.
