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Updated: May 20, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Comprehensive immunogenomic landscape analysis unveils CD33 + myeloid cell-driven immunomodulatory signatures in
Qinke Li1, Min Sheng2, Yiqian Chen3
1Department of Immunology, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400010, China; Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Background:
Understanding the causal relationships between immune cell populations and cancer development remains a critical challenge in tumor immunology.
Methods:
We employed Mendelian Randomization analysis leveraging genome-wide association studies of 612 immune cell traits and 91 cancer types to systematically evaluate causal associations. Single-cell RNA sequencing and computational deconvolution analyses were performed to characterize myeloid cell subpopulations in melanoma samples.
Findings:
Our analysis revealed significant relationships between specific immune cell subsets and cancer risk, particularly highlighting the role of CD33 + myeloid cells in melanoma pathogenesis. Single-cell RNA sequencing identified distinct CD33high myeloid subpopulations characterized by elevated expression of complement cascade components and chemokine signaling pathways. Through computational deconvolution of The Cancer Genome Atlas melanoma cohort, we demonstrated that elevated CD33high monocyte abundance correlates with increased immune dysfunction scores, reduced CD8 + T cell infiltration, and poor survival outcomes.
Interpretation:
Here we delineate the multifaceted mechanisms through which CD33 + myeloid cell populations orchestrate perturbations in the tumor-immune microenvironmental landscape, manifesting in compromised immunosurveillance and enhanced tumor progression. Our findings illuminate novel therapeutic opportunities through targeted modulation of myeloid cell function, while providing a systematic framework for understanding the complex interplay between immune cell populations and oncogenic processes.
