Please use this identifier to cite or link to this item:
https://doi.org/10.1182/blood-2018-01-829424
Title: | Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma | Authors: | Song, Tammy Linlin Nairismagi, Maarja-Liisa Laurensia, Yurike Lim, Jing-Quan Tan, Jing Li, Zhi-Mei Pang, Wan-Lu Kizhakeyil, Atish Wijaya, Giovani-Claresta Huang, Da-Chuan Nagarajan, Sanjanaa Chia, Burton Kuan-Hui Cheah, Daryl Liu, Yan-Hui Zhang, Fen Rao, Hui-Lan Tang, Tiffany Wong, Esther Kam-Yin Bei, Jin-Xin Iqbal, Jabed Grigoropoulos, Nicholas-Francis Ng, Siok-Bian Chng, Wee-Joo Teh, Bin-Tean Tan, Soo-Yong Verma, Navin Kumar Fan, Hao Lim, Soon-Thye Ong, Choon-Kiat |
Keywords: | Science & Technology Life Sciences & Biomedicine Hematology PERIPHERAL T-CELL CLASSICAL HODGKIN LYMPHOMA DEATH LIGAND 1 RECURRENT MUTATIONS SOMATIC MUTATIONS LEUKEMIC TRANSFORMATION GENETIC ALTERATIONS SIGNALING PATHWAYS JAK-STAT BLOCKADE |
Issue Date: | 13-Sep-2018 | Publisher: | AMER SOC HEMATOLOGY | Citation: | Song, Tammy Linlin, Nairismagi, Maarja-Liisa, Laurensia, Yurike, Lim, Jing-Quan, Tan, Jing, Li, Zhi-Mei, Pang, Wan-Lu, Kizhakeyil, Atish, Wijaya, Giovani-Claresta, Huang, Da-Chuan, Nagarajan, Sanjanaa, Chia, Burton Kuan-Hui, Cheah, Daryl, Liu, Yan-Hui, Zhang, Fen, Rao, Hui-Lan, Tang, Tiffany, Wong, Esther Kam-Yin, Bei, Jin-Xin, Iqbal, Jabed, Grigoropoulos, Nicholas-Francis, Ng, Siok-Bian, Chng, Wee-Joo, Teh, Bin-Tean, Tan, Soo-Yong, Verma, Navin Kumar, Fan, Hao, Lim, Soon-Thye, Ong, Choon-Kiat (2018-09-13). Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma. BLOOD 132 (11) : 1146-1158. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2018-01-829424 | Abstract: | Mature T-cell lymphomas, including peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTL), represent a heterogeneous group of non-Hodgkin lymphomas with dismal outcomes and limited treatment options. To determine the extent of involvement of the JAK/STAT pathway in this malignancy, we performed targeted capture sequencing of 188 genes in this pathway in 171 PTCL and NKTL cases. A total of 272 nonsynonymous somatic mutations in 101 genes were identified in 73% of the samples, including 258 single-nucleotide variants and 14 insertions or deletions. Recurrent mutations were most frequently located in STAT3 and TP53 (15%), followed by JAK3 and JAK1 (6%) and SOCS1 (4%). A high prevalence of STAT3 mutation (21%) was observed specifically in NKTL. Novel STAT3 mutations (p.D427H, E616G, p.E616K, and p.E696K) were shown to increase STAT3 phosphorylation and transcriptional activity of STAT3 in the absence of cytokine, in which p.E616K induced programmed cell death-ligand 1 (PD-L1) expression by robust binding of activated STAT3 to the PD-L1 gene promoter. Consistent with these findings, PD-L1 was overexpressed in NKTL cell lines harboring hotspot STAT3 mutations, and similar findings were observed by the overexpression of p.E616K and p.E616G in the STAT3 wild-type NKTL cell line. Conversely, STAT3 silencing and inhibition decreased PD-L1 expression in STAT3 mutant NKTL cell lines. In NKTL tumors, STAT3 activation correlated significantly with PD-L1 expression. We demonstrated that STAT3 activation confers high PD-L1 expression, which may promote tumor immune evasion. The combination of PD-1/PD-L1 antibodies and STAT3 inhibitors might be a promising therapeutic approach for NKTL, and possibly PTCL. | Source Title: | BLOOD | URI: | https://scholarbank.nus.edu.sg/handle/10635/207360 | ISSN: | 00064971 15280020 |
DOI: | 10.1182/blood-2018-01-829424 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
Song TL. Blood 2018. STAT3 drives PDL1 in ENKTL.pdf | Published version | 1.37 MB | Adobe PDF | CLOSED | Published |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.