DOI: 10.5061/dryad.b2rbnzspd
title: Single-cell profiling reveals immune-based mechanisms underlying tumor radiosensitization by a novel Mn porphyrin clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001)

description: 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 murine carcinoma model. Mice bearing 4T1 tumors were divided
 into 4 groups: control, MnBuOE, radiotherapy (RT), combined MnBuOE, and
 radiotherapy (MnBuOE/RT). In epithelial cells, epithelial-mesenchymal
 transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related
 genes were significantly downregulated in the MnBuOE/RT compared to the
 RT. All subtypes of cancer-associated fibroblasts (CAFs) were 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 than in the RT. Trajectory analysis showed that DC
 maturation-associated markers were increased in MnBuOE/RT. M1 macrophages
 were significantly increased in the MnBuOE/RT compared to the RT, whereas
 myeloid-derived suppressor cells were decreased. CellChat analysis showed
 that the number of cell-cell communications was the lowest in the
 MnBuOE/RT. 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.
description: # Single-cell profiling reveals immune-based mechanisms underlying tumor
 radiosensitization by a novel Mn porphyrin clinical candidate,
 MnTnBuOE-2-PyP5+ (BMX-001) 
 [https://doi.org/10.5061/dryad.b2rbnzspd](https://doi.org/10.5061/dryad.b2rbnzspd) The dataset comprises filtered matrices generated by CellRanger **(barcodes.tsv, features.tsv, matrix.mtx)**, along with single-cell annotated metadata **(Major_cell_annotations.txt)**, intended for publication in Antioxidants 2024 ## Descriptions ### **Single-cell sequencing data** \-  **barcodes.tsv**: the barcodes (unique cell-id) saved as TSV format that corresponds to 10x formats \-  **features.tsv**: the features/genes saved as TSV format that corresponds to 10x formats \-  **matrix.mtx**: the matrix files are stored in MTX  corresponding to 10x formats. \-  **Major_cell_annotations.txt**: a meta-data file is included that contains the following columns. \- **barcodes**: Contains unique cell barcodes. The prefix "Bx-Px" is concatenated in front of the barcodes, corresponding to batch names. \- **grid.ident**: Corresponding sample names. \- **Batch**: Contains batch names from B1 to B9 to create unique barcode names. \- **Sample**: Unique sample names, created by concatenating the group and time information (e.g., Group-Time). \- **Group**: Represents the experimental group, categorized as CN (control), MB (MnBuOE), RT (Radiotherapy), or MR (MnBuOE+RT). \- **Time**: Indicates the time after irradiation, specified as D10 or D15. \- **Cluster1**: Annotated cell clusters, divided into 10 major clusters: Macrophages/Monocytes, Neutrophils, T cells, DCs (pDC+cDC), Epithelial cells, Fibroblasts, Endothelial cells, Myocytes, and Stressful-MT. \- **Immune**: Categorized into immune cells and non-immune cells based on the annotations from Cluster1. ### R **Scripts for Analysis** \- **Global_celltype_annotations.R**: R script for global cell type annotations analysis. \- **Figurex_figure_scripts.R**: R scripts for generating manuscript figures. Each script is dedicated to a specific figure (e.g., Figure1_figure_scripts.R, Figure2_figure_scripts.R, etc.).