Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma
Resistance to anti-PD-1 immunotherapy remains a substantial challenge in R/R NKTL. In this study, we reported that combining DNMT inhibitors with anti-PD-1 mAb achieves a high complete response rate of 47.6% in immunotherapy-R/R NKTL patients. Mechanistically, DNMT inhibitors potentiate anti-PD-1 efficacy by triggering viral mimicry, remodeling the immune microenvironment and augmenting antitumor immunity.
Authors
- Anand D. Jeyasekharan (ORCID: https://orcid.org/0000-0001-9816-6137)
- Peili Wang (ORCID: https://orcid.org/0009-0008-3332-1480)
- Jing Han Hong (ORCID: https://orcid.org/0000-0002-2173-9192)
- Jing Ying Tan (ORCID: https://orcid.org/0000-0002-4605-4624)
- Dachuan Huang (ORCID: https://orcid.org/0000-0002-7518-4081)
- Soon Thye Lim (ORCID: https://orcid.org/0000-0002-0366-5505)
- Bin Tean Teh (ORCID: https://orcid.org/0000-0003-1514-1124)
- Jing Quan Lim (ORCID: https://orcid.org/0000-0003-3732-8707)
- Jason Yongsheng Chan (ORCID: https://orcid.org/0000-0002-4801-3703)
- Kelila Xin Ye Chai (ORCID: https://orcid.org/0000-0003-2912-6451)
- Xian Zeng (ORCID: https://orcid.org/0000-0001-5875-3599)
- Jin‐Xin Bei (ORCID: https://orcid.org/0000-0003-1333-407X)
- Peiyong Guan (ORCID: https://orcid.org/0000-0001-9958-0137)
- Yingxi Li (ORCID: https://orcid.org/0009-0007-4788-6282)
- Choon Kiat Ong (ORCID: https://orcid.org/0000-0001-6402-4288)
- Haixia He (ORCID: https://orcid.org/0000-0003-4614-6892)
- R. Xiao (ORCID: https://orcid.org/0000-0003-3245-3218)
- Jianfeng Chen (ORCID: https://orcid.org/0000-0002-4182-145X)
- Yali Wang (ORCID: https://orcid.org/0009-0004-8871-0150)
- Qiang Yu (ORCID: https://orcid.org/0000-0003-2132-8278)
- Huiqiang Huang (ORCID: https://orcid.org/0000-0002-9090-1907)
- Yan Gao (ORCID: https://orcid.org/0000-0002-1268-2999)
- Jiuping Gao (ORCID: https://orcid.org/0009-0007-0511-8867)
- Cheng Huang (ORCID: https://orcid.org/0000-0003-1358-6293)
- Yue Jiang
Institutions
- Sun Yat-sen University (CN)
- National University of Singapore (SG)
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Sun Yat-sen Memorial Hospital (CN)
- National University Cancer Institute, Singapore (SG)
- Duke-NUS Medical School (SG)
- National Cancer Centre Singapore (SG)
- Sun Yat-sen University Cancer Center (CN)
- Institutul Clinic Fundeni (RO)
- Genome Institute of Singapore (SG)
- Hainan Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1158/2159-8290.cd-25-0587
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Tanoto Foundation
- National Natural Science Foundation of China
- Medical Research Council
- National Medical Research Council
- National Key Research and Development Program of China