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Peer-reviewedCC BYFrontiers in oncology

Conditional myeloid-specific deletion of Ube2n hinders YUMM1.7 melanoma growth.

  • Kelsie Schiavone1
  • Adam Pecoraro1
  • Afsa Khawar1
  • Kathleen Zhang1
  • Vaibhav Jain2
  • Simon Gregory2
  • Daniel T Starczynowski3
  • Jennifer Y Zhang1,4
4 affiliations
  1. 1Department of Dermatology, Duke University Medical Center, Durham, NC, United States.
  2. 2Duke Molecular Physiology Institute, Durham, NC, United States.
  3. 3Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH, United States.
  4. 4Department of Pathology, Duke University Medical Center, Durham, NC, United States.
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Abstract

The role of UBE2N in myeloid cell-mediated immune suppression in cancer remains undefined. Here, we examined the function of UBE2N in myeloid cell-mediated tumor progression using a temporally inducible myeloid-specific knockout model (LysMCreERUbe2nfl/fl ). Temporally induced deletion of Ube2n in myeloid cells (Ube2nMyeKO ) significantly hindered growth of YUMM1.7 melanoma. This was accompanied by reduced myeloid cell burden within the tumor microenvironment. We observed altered abundance of PD-1, PD-L1, and SPP1 in the Ube2nMyeKO tumor microenvironment at the tissue level. In vitro analysis showed that knock-in expression of a catalytically deficient UBE2NC87S mutant in bone marrow-derived macrophages (BMDMs) markedly decreased expression of Spp1. We observed decreased SPP1 secretion in Ube2nMyeKO BMDM-conditioned media (CM). Treatment with Ube2nMyeKO BMDM-CM decreased co-expression of PD-1, TIM-3, and LAG-3 on chronically stimulated T cells. Antibody-mediated neutralization of SPP1 in Ube2nMyeWT BMDM-CM decreased PD-1 expression on CD8+ T cells. Together, these findings suggest a role for myeloid UBE2N in YUMM1.7 progression.

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Cite

BibTeXRIS
BibTeX
@article{schiavone2026conditional,
  title = {{Conditional myeloid-specific deletion of Ube2n hinders YUMM1.7 melanoma growth.}},
  author = {Kelsie Schiavone and Adam Pecoraro and Afsa Khawar and Kathleen Zhang and Vaibhav Jain and Simon Gregory and Daniel T Starczynowski and Jennifer Y Zhang},
  journal = {Frontiers in oncology},
  year = {2026},
  month = sep,
  doi = {10.3389/fonc.2026.1932270},
  url = {https://europepmc.org/article/MED/42851405},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Conditional myeloid-specific deletion of Ube2n hinders YUMM1.7 melanoma growth.
AU  - Kelsie Schiavone
AU  - Adam Pecoraro
AU  - Afsa Khawar
AU  - Kathleen Zhang
AU  - Vaibhav Jain
AU  - Simon Gregory
AU  - Daniel T Starczynowski
AU  - Jennifer Y Zhang
PY  - 2026
DA  - 2026/09/24
JO  - Frontiers in oncology
DO  - 10.3389/fonc.2026.1932270
UR  - https://europepmc.org/article/MED/42851405
AB  - The role of UBE2N in myeloid cell-mediated immune suppression in cancer remains undefined. Here, we examined the function of UBE2N in myeloid cell-mediated tumor progression using a temporally inducible myeloid-specific knockout model (LysMCreERUbe2nfl/fl ). Temporally induced deletion of Ube2n in myeloid cells (Ube2nMyeKO ) significantly hindered growth of YUMM1.7 melanoma. This was accompanied by reduced myeloid cell burden within the tumor microenvironment. We observed altered abundance of PD-1, PD-L1, and SPP1 in the Ube2nMyeKO tumor microenvironment at the tissue level. In vitro analysis showed that knock-in expression of a catalytically deficient UBE2NC87S mutant in bone marrow-derived macrophages (BMDMs) markedly decreased expression of Spp1. We observed decreased SPP1 secretion in Ube2nMyeKO BMDM-conditioned media (CM). Treatment with Ube2nMyeKO BMDM-CM decreased co-expression of PD-1, TIM-3, and LAG-3 on chronically stimulated T cells. Antibody-mediated neutralization of SPP1 in Ube2nMyeWT BMDM-CM decreased PD-1 expression on CD8+ T cells. Together, these findings suggest a role for myeloid UBE2N in YUMM1.7 progression.
SN  - 2234-943X
ER  -