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Unveiling major histocompatibility complex-mediated pan-cancer immune features by integrated single-cell and bulk RNA sequencing.
- Source :
-
Cancer letters [Cancer Lett] 2024 Aug 10; Vol. 597, pp. 217062. Date of Electronic Publication: 2024 Jun 13. - Publication Year :
- 2024
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Abstract
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet persistent challenges such as low response rate and significant heterogeneity necessitate attention. The pivotal role of the major histocompatibility complex (MHC) in ICI efficacy, its intricate impacts and potentials as a prognostic marker, warrants comprehensive exploration. This study integrates single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and spatial transcriptomic analyses to unveil pan-cancer immune characteristics governed by the MHC transcriptional feature (MHC.sig). Developed through scRNA-seq analysis of 663,760 cells across diverse cohorts and validated in 30 solid cancer types, the MHC.sig demonstrates a robust correlation between immune-related genes and infiltrating immune cells, highlighting its potential as a universal pan-cancer marker for anti-tumor immunity. Screening the MHC.sig for therapeutic targets using CRISPR data identifies potential genes for immune therapy synergy and validates its predictive efficacy for ICIs responsiveness across diverse datasets and cancer types. Finally, analysis of cellular communication patterns reveals interactions between C1QC <superscript>+</superscript> macrophages and malignant cells, providing insights into potential therapeutic agents and their sensitivity characteristics. This comprehensive analysis positions the MHC.sig as a promising marker for predicting immune therapy outcomes and guiding combinatorial therapeutic strategies.<br />Competing Interests: Declaration of competing interest All authors declare no potential conflicts of interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Sequence Analysis, RNA methods
Immune Checkpoint Inhibitors therapeutic use
Immune Checkpoint Inhibitors pharmacology
Biomarkers, Tumor genetics
Biomarkers, Tumor immunology
Gene Expression Profiling methods
Gene Expression Regulation, Neoplastic
Tumor Microenvironment immunology
Tumor Microenvironment genetics
RNA-Seq
Neoplasms genetics
Neoplasms immunology
Single-Cell Analysis methods
Major Histocompatibility Complex genetics
Major Histocompatibility Complex immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 597
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 38878852
- Full Text :
- https://doi.org/10.1016/j.canlet.2024.217062