Journal article
Gene signature reveals decreased SOX10-dependent transcripts in malignant cells from immune checkpoint inhibitor-resistant cutaneous melanomas
ISCIENCE, v 26(9), 107472
15 Sep 2023
PMID: 37636077
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Evidence is mounting for cross-resistance between immune checkpoint and targeted kinase inhibitor therapies in cutaneous melanoma patients. Since the loss of the transcription factor, SOX10, causes tolerance to MAPK pathway inhibitors, we used bioinformatic techniques to determine if reduced SOX10 expression/activity is associated with immune checkpoint inhibitor resistance. We integrated SOX10 ChIP-seq, knockout RNA-seq, and knockdown ATAC-seq data from melanoma cell models to develop a robust SOX10 gene signature. We used computational methods to validate this signature as a measure of SOX10-dependent activity in independent single-cell and bulk RNA-seq SOX10 knockdown, cell line panel, and MAPK inhibitor drug-resistant datasets. Evaluation of patient single cell RNA-seq data revealed lower levels of SOX10-dependent transcripts in immune checkpoint inhibitor-resistant tumors. Our results suggest that SOX10-deficient melanoma cells are associated with cross-resistance between targeted and immune checkpoint inhibitors and highlight the need to identify therapeutic strategies that target this subpopulation.
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Details
- Title
- Gene signature reveals decreased SOX10-dependent transcripts in malignant cells from immune checkpoint inhibitor-resistant cutaneous melanomas
- Publication Details
- ISCIENCE, v 26(9), 107472
- Publisher
- CELL PRESS; CAMBRIDGE
- Grant note
- This work is supported by grants from NIH/NCI (R01 CA196278 and R01 CA160495) to A.E. Aplin. CC is supported by American Cancer Society (130042-IRG-16-244-10-IRG), Melanoma Research Foundation, and Legacy of Hope Merit Award.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:001147822100001
- Scopus ID
- 2-s2.0-85167840882
- Other Identifier
- 991021861166404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology