期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01774
关键词
tumor cell-intrinsic programmed death 1; combinatorial immunotherapy; mammalian target of rapamycin; tumor growth; blockade
类别
资金
- National Key Research & Development (RD) Plan [2016YFC0906000, 2016YFC0906002]
- National Natural Science Foundation of China [81702969, 81572326, 81322036, 81272383, 81602518, 81502015, 81572303, 81530072, 81421001, 81320108024]
- Top-Notch Young Talents Program of China [ZTZ2015-48]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20152514]
- Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [15SG16]
- National Key Technology Support Program [2015BAI13B07]
- Shu Guang project
- SJTU-JX
Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are responsible for delivering inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1' s ligands PD-L1 and PD-L2 were found expressed in some tumor cells. However, recent studies revealed intrinsic expression of PD-1 in melanoma and some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1 expressed by tumor cells, modulating downstream mammalian target of rapamycin signaling and promoting tumor growth independent of adaptive immunity. In addition to melanoma, PD-1 was also detected in liver cancer cells as well as in non-small lung cancer cells. Unlike its oncogenic functions in melanoma and hepatic carcinoma cells, PD-1 seemed to play a distinct role in lung cancer, as blockade of PD-1 instead promoted tumor cells proliferation. Tumor-intrinsic PD-1 expression seems to be widespread in many tumor types, according to our reanalysis on cancer transcriptomic and proteomic data. The multifaceted roles of PD-1 in tumor cells beyond immune checkpoint signaling may explain the differential therapeutic effects of anti-PD-1 and anti-PD-L1 drugs and provide crucial information when developing combinatorial approaches to enhance antitumor immunity.
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