Evidence map›Paper›PMID 40187755›Full record

ArticleJournal for immunotherapy of cancer2025

β-blocker suppresses both tumoral sympathetic neurons and perivascular macrophages during oncolytic herpes virotherapy.

Konstantina Kyritsi, Rafal Pacholczyk, Eugene Douglass, Miao Yu, Hui Fang, Gang Zhou, Balveen Kaur, Qin Wang, David H Munn, Bangxing Hong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Konstantina KyritsiDepartment of Pathology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.
Rafal PacholczykDepartment of Biochemistry and Molecular Biology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.
Eugene DouglassDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA.
Miao YuGenomics core, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.
Hui FangDepartment of Biochemistry and Molecular Biology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.
Gang ZhouDepartment of Biochemistry and Molecular Biology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.ORCID http://orcid.org/0000-0001-8967-114X
Balveen KaurDepartment of Pathology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.ORCID http://orcid.org/0000-0001-7738-0804
Qin WangDepartment of Neuroscience & Regenerative Medicine, Augusta University, Augusta, Georgia, USA.
David H MunnDepartment of Pediatrics, Pediatric Immunotherapy Program, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA.
Bangxing HongDepartment of Pathology, Georgia Cancer Center at Augusta University, Augusta, Georgia, USA bhong@augusta.edu.ORCID http://orcid.org/0000-0001-7458-0480

Funding

Reprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0M
Targeting CD44 signaling in regulating glioblastoma stemness and immune responseR21NS130429 · NINDS · AUGUSTA UNIVERSITY · PI HONG, BANGXING B · 2023 to 2024
$433k
NCI NIH HHS R01 CA103320NINDS NIH HHS R21 NS130429
6 · The paper itself

Abstract

backgroundThe autonomic nervous system (ANS) plays a key role in regulating tumor development and therapy resistance in various solid tumors. Within the ANS, the sympathetic nervous system (SNS) is typically associated with protumor effects. However, whether the SNS influences the antitumor efficacy of intratumoral injections of oncolytic herpes simplex virus (oHSV) in solid tumors remains unknown.

methodsIn this study, we examined SNS innervation and its interaction with immune cell infiltration in both human and murine triple-negative breast cancer models during intratumoral oHSV injections and SNS blockade on oHSV's antitumor activity.

resultsIntratumor oHSV injection promotes SNS innervation accompanied by CD45+cell infiltration in both the human MDA-MB-468 orthotopic model and the murine 4T1 mammary tumor model. Mechanistically, tumor-secreted factors vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β) and transcription factors (CREB, AP-1, MeCP2, and REST), which promote SNS innervation, were found to be upregulated in oHSV-treated tumors. Combining the SNS antagonist, a β-blocker, with oHSV significantly increased immune cell infiltration, particularly CD8+T cells in oHSV-treated 4T1 tumors. Single-cell messenger RNA sequencing revealed that oHSV injection upregulated a specific population of perivascular macrophages (pvMacs) expressing high levels of VEGFA, CD206, CCL3, and CCL4, which suppress T-cell activation. The use of a β-blocker reduced the infiltration of oHSV-induced pvMacs, transition to inflammatory macrophages expressing Hexb, enhancing the diversity of T-cell receptor clonotypes. Further analysis suggested that TGF-β signaling within the tumor partially mediates SNS activation in the 4T1 model.

conclusionOur findings demonstrate that combining a β-blocker with oHSV significantly enhances the antitumor efficacy of oHSV in breast cancer by targeting TGF-β-mediated SNS innervation and immunosuppression.

Indexed as

Adrenergic beta-AntagonistsMacrophagesOncolytic VirotherapyOncolytic VirusesSympathetic Nervous SystemAnimalsCell Line, TumorFemaleHumansMiceAdrenergic beta-AntagonistsBreast CancerImmunosuppressionMacrophageOncolytic virusTumor microenvironment - TME

Identifiers

PMID40187755
PMCPMC11973798

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.