Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge Article Swipe
Tingting Qin
,
Austin K. Mattox
,
Jean S. Campbell
,
Jong Chul Park
,
Kee-Young Shin
,
Shiting Li
,
Peter M. Sadow
,
William C. Faquin
,
Goran Micevic
,
Andrew J. Daniels
,
Robert I. Haddad
,
Christopher Garris
,
Mikaël J. Pittet
,
Thorsten R. Mempel
,
Anne O’Neill
,
Maureen A. Sartor
,
Sara I. Pai
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1172/jci181671
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1172/jci181671
BACKGROUNDImmune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, the majority of patients are refractory.METHODSIn a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days in combination with durvalumab and tremelimumab after progression on ICB. The primary objective was to assess the biologically effective dose of 5-aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety.RESULTSThirty-eight percent (3 of 8) of participants with evaluable paired tissue samples had a greater-than 2-fold increase from baseline in IFN-γ signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA), 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%), and 58% (7 of 12) of treated participants demonstrated prolonged OS of greater than 12 months.CONCLUSIONOur findings suggest that low-dose 5-aza can reprogram systemic host immune responses and the local TME to increase IFN-γ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon ICB rechallenge.TRIAL REGISTRATIONClinicalTrials.gov NCT03019003.FUNDINGNIH/NCI P01 CA240239.
Related Topics
Concepts
Immunotherapy
Refractory (planetary science)
Medicine
Head and neck
Epigenetics
Epigenetic therapy
Oncology
Cancer research
Immunology
Internal medicine
Immune system
DNA methylation
Surgery
Biology
Gene
Gene expression
Biochemistry
Astrobiology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci181671
- http://www.jci.org/articles/view/181671/files/pdf
- OA Status
- gold
- Cited By
- 9
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4408491186
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4408491186Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci181671Digital Object Identifier
- Title
-
Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallengeWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-03-16Full publication date if available
- Authors
-
Tingting Qin, Austin K. Mattox, Jean S. Campbell, Jong Chul Park, Kee-Young Shin, Shiting Li, Peter M. Sadow, William C. Faquin, Goran Micevic, Andrew J. Daniels, Robert I. Haddad, Christopher Garris, Mikaël J. Pittet, Thorsten R. Mempel, Anne O’Neill, Maureen A. Sartor, Sara I. PaiList of authors in order
- Landing page
-
https://doi.org/10.1172/jci181671Publisher landing page
- PDF URL
-
https://www.jci.org/articles/view/181671/files/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.jci.org/articles/view/181671/files/pdfDirect OA link when available
- Concepts
-
Immunotherapy, Refractory (planetary science), Medicine, Head and neck, Epigenetics, Epigenetic therapy, Oncology, Cancer research, Immunology, Internal medicine, Immune system, DNA methylation, Surgery, Biology, Gene, Gene expression, Biochemistry, AstrobiologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 9Per-year citation counts (last 5 years)
- References (count)
-
51Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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