Journal Article

Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice

Lau, Janet, McBride, Jacqueline, Yauch, Robert, Sanders, Laura, Grogan, Jane, Irving, Bryan, Javinal, Vincent, Totpal, Klara, Chiu, Henry, Belvin, Marcia, Schmidt, Maike, Hong, Rebecca, Koeppen, Hartmut, Mellman, Ira, Haley, Benjamin, Kim, Jeong M., Cheung, Jeanne, Navarro, Armando, Lianoglou, Steve, Caplazi, Patrick

2017

Overview

Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis. PD-L1, the ligand for T-cell inhibitory receptor PD-1, can be expressed by various cell types in the tumour microenvironment. Here, the authors show that, in mouse models, the expression of PD-L1 from both cancerous and normal host immune cells is important for suppressing anti-tumour immune responses.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 13/31 / 13/51 / 38/39 / 38/88 / 38/90 / 631/250/251 / 631/67/580 / 64 / 64/60 / 82/1 / 82/80 / Animals / Antibodies / Antibodies, Blocking - pharmacology / B7-H1 Antigen - antagonists & inhibitors / B7-H1 Antigen - genetics / B7-H1 Antigen - immunology / Cell Line, Tumor / Cells / Cytotoxicity / Humanities and Social Sciences / Humans / Immune system / Immunotherapy / Ligands / Lung cancer / Mice, Knockout / multidisciplinary / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - immunology / Oncology / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Programmed Cell Death 1 Receptor - immunology / Science / Science (multidisciplinary) / Signal Transduction - drug effects / Signal Transduction - genetics / Signal Transduction - immunology / T-Lymphocytes, Cytotoxic - drug effects / T-Lymphocytes, Cytotoxic - immunology / T-Lymphocytes, Cytotoxic - metabolism / Tumor Microenvironment - drug effects / Tumor Microenvironment - genetics / Tumor Microenvironment - immunology / Tumors