Title |
KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma
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Published in |
Cancer Immunology, Immunotherapy, April 2017
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DOI | 10.1007/s00262-017-2005-z |
Pubmed ID | |
Authors |
Nan Chen, Wenfeng Fang, Zhong Lin, Peijian Peng, Juan Wang, Jianhua Zhan, Shaodong Hong, Jiaxing Huang, Lin Liu, Jin Sheng, Ting Zhou, Ying Chen, Hongyu Zhang, Li Zhang |
Abstract |
It was reported that PD-L1 expression was correlated with genetic alterations. Whether PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) in non-small-cell lung cancer (NSCLC) and the underlying molecular mechanism were largely unknown. In this study, we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 expression was associated with KRAS mutation both in the human lung adenocarcinoma cell lines and tissues. PD-L1 was up-regulated by KRAS mutation through p-ERK but not p-AKT signaling. We also found that KRAS-mediated up-regulation of PD-L1 induced the apoptosis of CD3-positive T cells which was reversed by anti-PD-1 antibody (Pembrolizumab) or ERK inhibitor. PD-1 blocker or ERK inhibitor could recover the anti-tumor immunity of T cells and decrease the survival rates of KRAS-mutant NSCLC cells in co-culture system in vitro. However, Pembrolizumab combined with ERK inhibitor did not show synergistic effect on killing tumor cells in co-culture system. Our study demonstrated that KRAS mutation could induce PD-L1 expression through p-ERK signaling in lung adenocarcinoma. Blockade of PD-1/PD-L1 pathway may be a promising therapeutic strategy for human KRAS-mutant lung adenocarcinoma. |
X Demographics
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Mexico | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 166 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 26 | 16% |
Student > Bachelor | 25 | 15% |
Student > Ph. D. Student | 23 | 14% |
Student > Master | 16 | 10% |
Other | 13 | 8% |
Other | 18 | 11% |
Unknown | 45 | 27% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 43 | 26% |
Biochemistry, Genetics and Molecular Biology | 34 | 20% |
Agricultural and Biological Sciences | 10 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 5% |
Chemistry | 4 | 2% |
Other | 14 | 8% |
Unknown | 52 | 31% |