期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 12, 页码 6640-6650出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1921445117
关键词
tumor cell-intrinsic PD-1; tumor cell-intrinsic PD-L1; biomarker; tumor suppressor; drug resistance
资金
- Strategic Pilot Science and Technology Project of the Chinese Academy of Sciences [XDB29040103]
- Frontier Research Program of the Chinese Academy of Sciences [QYZDB-SSW-SMC038]
- National Natural Science Foundation of China (NSFC) [81773023, 81802526]
- National Key Research and Development (R&D) Program of China [2016YFC1302103]
- Technological Innovation Project of Shanxi Transformation and Comprehensive Reform Demonstration Zone [2017KJCX01]
- One-Hundred Talent of Shanxi Province
The programmed cell death 1 (PD-1) receptor on the surface of immune cells is an immune checkpoint molecule that mediates the immune escape of tumor cells. Consequently, antibodies targeting PD-1 have shown efficacy in enhancing the antitumor activity of T cells in some types of cancers. However, the potential effects of PD-1 on tumor cells remain largely unknown. Here, we show that PD-1 is expressed across a broad range of tumor cells. The silencing of PD-1 or its ligand, PD-1 ligand 1 (PD-L1), promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Conversely, overexpression of PD-1 or PD-L1 inhibits tumor cell proliferation and colony formation. Moreover, blocking antibodies targeting PD-1 or PD-L1 promote tumor growth in cell cultures and xenografts. Mechanistically, the coordination of PD-1 and PD-L1 activates its major downstream signaling pathways including the AKT and ERK1/2 pathways, thus enhancing tumor cell growth. This study demonstrates that PD-1/PD-L1 is a potential tumor suppressor and potentially regulates the response to anti-PD-1/ PD-L1 treatments, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.
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