| Autor: |
Nupur Nigam, Benjamin Bernard, Samantha Sevilla, Sohyoung Kim, Mohd Saleem Dar, Daniel Tsai, Yvette Robbins, Kyunghee Burkitt, Cem Sievers, Clint T. Allen, Richard L. Bennett, Theophilus T. Tettey, Benjamin Carter, Lorenzo Rinaldi, Mark W. Lingen, Houssein Sater, Elijah F. Edmondson, Arfa Moshiri, Abbas Saeed, Hui Cheng, Xiaolin Luo, Kevin Brennan, Vishal Koparde, Chen Chen, Sudipto Das, Thorkell Andresson, Abdalla Abdelmaksoud, Madhavi Murali, Seiji Sakata, Kengo Takeuchi, Raj Chari, Yusuke Nakamura, Ravindra Uppaluri, John B. Sunwoo, Carter Van Waes, Jonathan D. Licht, Gordon L. Hager, Vassiliki Saloura |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 42, Iss 7, Pp 112823- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112823 |
| Popis: |
Summary: Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8+ T cells and increases sensitivity to anti-programmed death 1 (PD-1) therapy. SMYD3 overexpression is associated with decreased CD8 T cell infiltration and poor response to neoadjuvant pembrolizumab. These data support combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in HPV-negative HNSCC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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