Title |
Down Regulation of c-FLIPL Enhance PD-1 Blockade Efficacy in B16 Melanoma
|
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Published in |
Frontiers in oncology, September 2019
|
DOI | 10.3389/fonc.2019.00857 |
Pubmed ID | |
Authors |
Yao Wang, Jing-jing Li, Hong-jun Ba, Ke-feng Wang, Xi-zhi Wen, Dan-dan Li, Xiao-feng Zhu, Xiao-shi Zhang |
Abstract |
Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients. Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma. We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model. Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. Moreover, knockdown of c-FLIPL could decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment. Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Switzerland | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 2 | 13% |
Student > Master | 2 | 13% |
Student > Doctoral Student | 1 | 6% |
Student > Bachelor | 1 | 6% |
Researcher | 1 | 6% |
Other | 2 | 13% |
Unknown | 7 | 44% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 3 | 19% |
Medicine and Dentistry | 2 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
Immunology and Microbiology | 1 | 6% |
Agricultural and Biological Sciences | 1 | 6% |
Other | 0 | 0% |
Unknown | 8 | 50% |