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Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001).

Publication ,  Journal Article
Noh, SU; Lim, J; Shin, S-W; Kim, Y; Park, W-Y; Batinic-Haberle, I; Choi, C; Park, W
Published in: Antioxidants (Basel, Switzerland)
April 2024

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in a murine carcinoma model. Mice bearing 4T1 tumors were divided into four groups: control, MnBuOE, radiotherapy (RT), and combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, the epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT group compared with the RT group. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT group than in the RT group. Trajectory analysis showed that dendritic cells maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT group compared with the RT group, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT group. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001, from the perspective of each cell type within the tumor microenvironment.

Duke Scholars

Published In

Antioxidants (Basel, Switzerland)

DOI

EISSN

2076-3921

ISSN

2076-3921

Publication Date

April 2024

Volume

13

Issue

4

Start / End Page

477

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

Citation

APA
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MLA
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Noh, S. U., Lim, J., Shin, S.-W., Kim, Y., Park, W.-Y., Batinic-Haberle, I., … Park, W. (2024). Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001). Antioxidants (Basel, Switzerland), 13(4), 477. https://doi.org/10.3390/antiox13040477
Noh, Sun Up, Jinyeong Lim, Sung-Won Shin, Yeeun Kim, Woong-Yang Park, Ines Batinic-Haberle, Changhoon Choi, and Won Park. “Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001).Antioxidants (Basel, Switzerland) 13, no. 4 (April 2024): 477. https://doi.org/10.3390/antiox13040477.
Noh SU, Lim J, Shin S-W, Kim Y, Park W-Y, Batinic-Haberle I, et al. Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001). Antioxidants (Basel, Switzerland). 2024 Apr;13(4):477.
Noh, Sun Up, et al. “Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001).Antioxidants (Basel, Switzerland), vol. 13, no. 4, Apr. 2024, p. 477. Epmc, doi:10.3390/antiox13040477.
Noh SU, Lim J, Shin S-W, Kim Y, Park W-Y, Batinic-Haberle I, Choi C, Park W. Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001). Antioxidants (Basel, Switzerland). 2024 Apr;13(4):477.

Published In

Antioxidants (Basel, Switzerland)

DOI

EISSN

2076-3921

ISSN

2076-3921

Publication Date

April 2024

Volume

13

Issue

4

Start / End Page

477

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology