---
title: "BRD9–PTGES/PGE2 Axis as an Immune‑Sensitising Vulnerability in Ovarian Cancer"
id: "pubmed-42349121"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42349121"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42349121/"
doi: "10.1016/j.bbrc.2026.154180"
published_at: "2026-09-03T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# BRD9–PTGES/PGE2 Axis as an Immune‑Sensitising Vulnerability in Ovarian Cancer
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42349121
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42349121/)
- **DOI:** [10.1016/j.bbrc.2026.154180](https://doi.org/10.1016%2Fj.bbrc.2026.154180)
- **Published At:** 2026-09-03T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Ovarian cancer is poorly responsive to immune checkpoint blockade, implying tumor-intrinsic programs suppress T cell–mediated antitumor activity. - Investigators developed an MHC-independent, B7H3×CD3 redirected cytotoxicity platform that produces a reproducible partial-kill window to reveal immune-sensitizing perturbations under fixed recognition conditions. - A screen of 1,796 bioactive compounds in paired SKOV3 monocultures and SKOV3/PBMC co-cultures separated direct cytotoxics from immune-sensitizing agents. - The selective bromodomain inhibitor **I‑BRD9** (targeting **BRD9**) emerged as a top immune-sensitizing hit that enhanced T cell–mediated killing in ovarian cancer models, B7‑H3–positive cell lines, and patient-derived tumor suspensions. - I‑BRD9 did not reduce viability of tumor cells or PBMCs, indicating a modulation of immune sensitivity rather than direct cytotoxicity. - Cross-cell–line RNA-seq after BRD9 inhibition identified a coordinated tumor-intrinsic immune resistance program involving **PTGES/PGE2** biosynthesis, inhibitory ligands, chemokines that attract T cells, antigen-presentation transcripts, and extracellular matrix features. - siRNA knockdown of **PTGES** recapitulated key actions of BRD9 inhibition: restoring chemokine/PGE2-axis transcripts, promoting CD8+ T‑cell proliferation and IFN-γ production, and increasing expression of T‑cell effector–associated genes. - The data nominate a tumor-intrinsic **BRD9–PTGES/PGE2 axis** as an actionable pathway limiting ovarian cancer sensitivity to T cell cytotoxicity and a potential target to sensitize tumors to redirected T‑cell killing. - Authors declared no competing financial interests or relationships.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jun 23. # Redirected T-cell cytotoxicity identifies BRD9-PTGES axis as an immune-sensitising vulnerability in ovarian cancer [Shanni Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+S&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Peng Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+P&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Changrui Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+C&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Shuyi Qian](https://pubmed.ncbi.nlm.nih.gov/?term=Qian+S&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Fan Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+F&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Xia Yin](https://pubmed.ncbi.nlm.nih.gov/?term=Yin+X&cauthor_id=42349121)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-2 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yinxia2@aliyun.com."), [Bowen Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+B&cauthor_id=42349121)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#full-view-affiliation-3 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: sunbw1226@126.com.") Affiliations Expand ### Affiliations * 1 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. * 2 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yinxia2@aliyun.com. * 3 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: sunbw1226@126.com. * PMID: **42349121** * DOI: [ 10.1016/j.bbrc.2026.154180 ](https://doi.org/10.1016/j.bbrc.2026.154180) Item in Clipboard # Redirected T-cell cytotoxicity identifies BRD9-PTGES axis as an immune-sensitising vulnerability in ovarian cancer Shanni Guo et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42349121/) . 2026 Sep 3:829:154180. doi: 10.1016/j.bbrc.2026.154180. Epub 2026 Jun 23. ### Authors [Shanni Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+S&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Peng Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+P&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Changrui Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+C&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Shuyi Qian](https://pubmed.ncbi.nlm.nih.gov/?term=Qian+S&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Fan Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+F&cauthor_id=42349121)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-1 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Xia Yin](https://pubmed.ncbi.nlm.nih.gov/?term=Yin+X&cauthor_id=42349121)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-2 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yinxia2@aliyun.com."), [Bowen Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+B&cauthor_id=42349121)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42349121/#short-view-affiliation-3 "Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: sunbw1226@126.com.") ### Affiliations * 1 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. * 2 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yinxia2@aliyun.com. * 3 Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: sunbw1226@126.com. * PMID: **42349121** * DOI: [ 10.1016/j.bbrc.2026.154180 ](https://doi.org/10.1016/j.bbrc.2026.154180) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Ovarian cancer shows limited responsiveness to immune checkpoint blockade, suggesting that malignant cells harbor intrinsic programs capable of suppressing T cell-mediated antitumor immunity. To uncover these programs under fixed recognition signal conditions, the research team established and optimized a B7H3×CD3-based, MHC-independent redirected cytotoxicity platform, which generated a reproducible partial-killing window. By screening 1796 bioactive compounds in paired SKOV3 monocultures and SKOV3/PBMC co-cultures, the researchers distinguished immune-sensitizing perturbations from direct cytotoxic agents and identified I-BRD9, a selective BRD9 bromodomain inhibitor, as a top candidate. I-BRD9 enhanced T cell-mediated killing in ovarian cancer models, B7-H3-positive benchmark cell lines, and patient-derived ovarian tumor suspensions, without affecting tumor cell or PBMC viability. Cross-cell line RNA-seq analysis revealed that BRD9 inhibition reshapes a coordinated immune resistance program involving PGE2 biosynthesis, inhibitory ligands, T cell-attracting chemokines, antigen presentation-related transcripts, and extracellular matrix features. Within this program, siRNA-mediated PTGES knockdown functionally recapitulated key effects of I-BRD9 by restoring chemokine/PGE2-axis transcripts, promoting CD8+ T-cell proliferation and IFN-γ production, and enhancing T-cell effector-associated gene expression. These findings establish the BRD9-PTGES/PGE2 axis as an actionable tumor-intrinsic pathway that limits ovarian cancer sensitivity to T cell-mediated cytotoxicity. **Keywords:** BRD9; Immune sensitization; Ovarian cancer; PTGES/PGE2; Redirected T-cell cytotoxicity. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Comparison of the cytotoxic response against ovarian cancer by immune effector cells isolated and expanded from normal donors and ovarian cancer patients. ](https://pubmed.ncbi.nlm.nih.gov/22409787/) Ingersoll SB, Stoltzfus GP, Merchant MH, Ahmad S, Edwards CR, Ahmed A, Oyer JL, Finkler NJ, Holloway RW, Edwards JR.Ingersoll SB, et al.Cytotherapy. 2012 Jul;14(6):716-23. doi: 10.3109/14653249.2012.663484. Epub 2012 Mar 12.Cytotherapy. 2012.PMID: 22409787 * [ PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer. ](https://pubmed.ncbi.nlm.nih.gov/24586709/) Guo Z, Wang X, Cheng D, Xia Z, Luan M, Zhang S.Guo Z, et al.PLoS One. 2014 Feb 27;9(2):e89350. doi: 10.1371/journal.pone.0089350. eCollection 2014.PLoS One. 2014.PMID: 24586709Free PMC article. * [ Combined targeting of mesothelin and tenascin-C enhances CAR-T cell function and tumor microenvironment modulation in ovarian cancer. ](https://pubmed.ncbi.nlm.nih.gov/42259008/) Wang X, Zhang D, Wang T, Li X, Zhang J.Wang X, et al.Mol Immunol. 2026 Aug;196:35-43. doi: 10.1016/j.molimm.2026.05.010. Epub 2026 Jun 8.Mol Immunol. 2026.PMID: 42259008 * [ Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells. ](https://pubmed.ncbi.nlm.nih.gov/29699516/) Morrison BJ, Steel JC, Morris JC.Morrison BJ, et al.BMC Cancer. 2018 Apr 26;18(1):469. doi: 10.1186/s12885-018-4389-3.BMC Cancer. 2018.PMID: 29699516Free PMC article. * [ Follicular T cells in the ovarian cancer immune microenvironment: biological insights and translational implications. ](https://pubmed.ncbi.nlm.nih.gov/42311678/) Xu Y, Li L.Xu Y, et al.Front Immunol. 2026 Jun 2;17:1849305. doi: 10.3389/fimmu.2026.1849305. eCollection 2026.Front Immunol. 2026.PMID: 42311678Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42349121) ## MeSH terms * Bromodomain Containing Proteins Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bromodomain+Containing+Proteins%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Bromodomain+Containing+Proteins) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42349121/) * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5
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