---
title: "ADAR1 Loss in Pancreatic Cancer Enhances cDC1 Activation and Sensitizes Tumors to Immunotherapy"
id: "pubmed-42308348"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42308348"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42308348/"
doi: "10.1158/2326-6066.CIR-25-1626"
published_at: "2026-09-02T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# ADAR1 Loss in Pancreatic Cancer Enhances cDC1 Activation and Sensitizes Tumors to Immunotherapy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42308348
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42308348/)
- **DOI:** [10.1158/2326-6066.CIR-25-1626](https://doi.org/10.1158%2F2326-6066.CIR-25-1626)
- **Published At:** 2026-09-02T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Pancreatic cancer shows poor response to immunotherapy largely because of inadequate **CD8+ T-cell** priming and limited T-cell infiltration into tumors. Enhancing T-cell priming is therefore a key therapeutic objective. - The RNA-editing enzyme **ADAR1** is important for immune homeostasis; the study reported a positive correlation between **ADAR1** expression and pancreatic cancer progression. - Genetic or functional depletion of **ADAR1** in tumor cells caused excessive production of **interferon β (IFNβ)**. - Increased **IFNβ** following ADAR1 loss led to a higher abundance and activation state of conventional type 1 dendritic cells (**cDC1**), cellular mediators crucial for cross-priming CD8+ T cells. - The rise in activated **cDC1** was associated with enhanced recruitment and activation of **CD8+ T cells** within the tumor microenvironment. - These immune changes sensitized pancreatic tumors to immunotherapy, indicating **ADAR1 inhibition combined with immunotherapy** may be a promising therapeutic strategy. - The abstract reports these key mechanistic links but does not provide experimental details, quantitative results, or specific immunotherapy modalities tested; such information was not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42308348/#linkout) Title & authors Abstract Similar articles MeSH terms Substances Related information Grants and funding LinkOut - more resources Cancer Immunol Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Immunol+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Immunol+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) . 2026 Sep 2;14(9):1386-1399. doi: 10.1158/2326-6066.CIR-25-1626. # ADAR1 Deficiency in Pancreatic Cancer Cells Potentiates cDC1 Activation and Promotes Sensitization to Immunotherapy [Botai Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+B&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China."), [Xiaoshuang Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+X&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Bowen Xie](https://pubmed.ncbi.nlm.nih.gov/?term=Xie+B&cauthor_id=42308348)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Xuan Zhong](https://pubmed.ncbi.nlm.nih.gov/?term=Zhong+X&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Peng Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+P&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Xinyi Lou](https://pubmed.ncbi.nlm.nih.gov/?term=Lou+X&cauthor_id=42308348)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-4 "School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China."), [Ting Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+T&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China."), [Chen Dong](https://pubmed.ncbi.nlm.nih.gov/?term=Dong+C&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#full-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.") Affiliations Expand ### Affiliations * 1 Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China. * 2 Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China. * 3 Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. * 4 School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. * PMID: **42308348** * DOI: [ 10.1158/2326-6066.CIR-25-1626 ](https://doi.org/10.1158/2326-6066.cir-25-1626) Item in Clipboard # ADAR1 Deficiency in Pancreatic Cancer Cells Potentiates cDC1 Activation and Promotes Sensitization to Immunotherapy Botai Li et al. Cancer Immunol Res. 2026. Show details Display options Display options Format Abstract PubMed PMID Cancer Immunol Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Immunol+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Immunol+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) . 2026 Sep 2;14(9):1386-1399. doi: 10.1158/2326-6066.CIR-25-1626. ### Authors [Botai Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+B&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China."), [Xiaoshuang Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+X&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Bowen Xie](https://pubmed.ncbi.nlm.nih.gov/?term=Xie+B&cauthor_id=42308348)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Xuan Zhong](https://pubmed.ncbi.nlm.nih.gov/?term=Zhong+X&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Peng Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+P&cauthor_id=42308348)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-3 "Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China."), [Xinyi Lou](https://pubmed.ncbi.nlm.nih.gov/?term=Lou+X&cauthor_id=42308348)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-4 "School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China."), [Ting Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+T&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China."), [Chen Dong](https://pubmed.ncbi.nlm.nih.gov/?term=Dong+C&cauthor_id=42308348)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-1 "Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42308348/#short-view-affiliation-2 "Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China.") ### Affiliations * 1 Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine - Affiliated Renji Hospital, Shanghai, China. * 2 Westlake University School of Medicine, New Cornerstone Science Laboratory, Hangzhou, China. * 3 Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. * 4 School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. * PMID: **42308348** * DOI: [ 10.1158/2326-6066.CIR-25-1626 ](https://doi.org/10.1158/2326-6066.cir-25-1626) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Pancreatic cancer responds poorly to immunotherapy, primarily due to poor activation of CD8+ T cells and their limited infiltration into the tumor tissue. Strategies to enhance CD8+ T-cell priming and function are therefore critical for improving immunotherapeutic efficacy in pancreatic cancer. The RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) plays a pivotal role in maintaining immune homeostasis. In this study, we found that ADAR1 expression positively correlates with pancreatic cancer progression. Depletion of ADAR1 in tumor cells resulted in excessive production of interferon β, which increased the abundance and activation of conventional type 1 dendritic cells. This alteration enhanced CD8+ T-cell recruitment and activation, ultimately sensitizing pancreatic cancer to immunotherapy. Collectively, our findings support ADAR1 inhibition combined with immunotherapy as a promising therapeutic strategy for pancreatic cancer. ©2026 American Association for Cancer Research. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Depletion of the RNA-Editing Enzyme ADAR1 Invigorates the Antitumor Immunity of NK Cells. ](https://pubmed.ncbi.nlm.nih.gov/41560319/) Chen S, Lu D, Liang R, Tan W, Zhao E, Wu S, Li X, Song Y, Wan M, Xie X, Zhang Q, Liu Q.Chen S, et al.Adv Sci (Weinh). 2026 May;13(29):e17216. doi: 10.1002/advs.202517216. Epub 2026 Jan 20.Adv Sci (Weinh). 2026.PMID: 41560319Free PMC article. * [ Tumor-secreted AGR2 induces dendritic cell dysfunction and impairs immunotherapy efficacy in LKB1-deficient cancer. ](https://pubmed.ncbi.nlm.nih.gov/41135949/) Yao Y, Luo Y, Wang Z, Yin E, Liu C, Zheng S, Wang X, Tang X, Sun N, He J.Yao Y, et al.J Immunother Cancer. 2025 Oct 23;13(10):e012710. doi: 10.1136/jitc-2025-012710.J Immunother Cancer. 2025.PMID: 41135949Free PMC article. * [ Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer. ](https://pubmed.ncbi.nlm.nih.gov/36343976/) Gomez S, Cox OL, Walker RR 3rd, Rentia U, Hadley M, Arthofer E, Diab N, Grundy EE, Kanholm T, McDonald JI, Kobyra J, Palmer E, Noonepalle S, Villagra A, Leitenberg D, Bollard CM, Saunthararajah Y, Chiappinelli KB.Gomez S, et al.J Immunother Cancer. 2022 Nov;10(11):e004974. doi: 10.1136/jitc-2022-004974.J Immunother Cancer. 2022.PMID: 36343976Free PMC article. * [ Chemokine-chemokine receptor networks in conventional type I dendritic cells: an opportunity to prime and boost anticancer immunity. ](https://pubmed.ncbi.nlm.nih.gov/41135412/) Kuo N, Shinn CK, Schokrpur S, Idoyaga J, Handel T, Gutkind JS.Kuo N, et al.J Pharmacol Exp Ther. 2025 Nov;392(11):103725. doi: 10.1016/j.jpet.2025.103725. Epub 2025 Sep 25.J Pharmacol Exp Ther. 2025.PMID: 41135412Free PMC article.Review. * [ Orchestrating innate immunity through RNA editing and helicase activity: ADAR1, dsRNA sensors, and tumor immune evasion. ](https://pubmed.ncbi.nlm.nih.gov/42058149/) Minakuchi M, Salvino JM, Villanueva J.Minakuchi M, et al.Front Cell Dev Biol. 2026 Apr 14;14:1788799. doi: 10.3389/fcell.2026.1788799. eCollection 2026.Front Cell Dev Biol. 2026.PMID: 42058149Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42308348) ## MeSH terms * Adenosine Deaminase* / deficiency Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenosine+Deaminase%2Fdeficiency%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenosine+Deaminase) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * Adenosine Deaminase* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenosine+Deaminase%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenosine+Deaminase) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * Adenosine Deaminase* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenosine+Deaminase%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenosine+Deaminase) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * CD8-Positive T-Lymphocytes / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22CD8-Positive+T-Lymphocytes%2Fimmunology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=CD8-Positive+T-Lymphocytes) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42308348/) * Dendritic Cells* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dendritic+Cells%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dendritic+Cells) * [ Add to Search ](https:
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