2023 World Conference on Lung Cancer (Posters)-P2.21. Single-Cell Dissection Reveals Mesothelial Heterogeneity and Dysfunctional Immunity in Malignant Pleural Mesothelioma

P2.21. Single-Cell Dissection Reveals Mesothelial Heterogeneity and Dysfunctional Immunity in Malignant Pleural Mesothelioma - PDF(Abstract)

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This study aimed to understand the cellular heterogeneity and dysfunctional immunity in malignant pleural mesothelioma (MPM). The researchers analyzed the single-cell transcriptome of the human pleural mesothelium to decipher the cellular ecosystem. They identified 15 clusters, including stromal cells, mesothelial cells, monocytes, and macrophages. A subset of mesothelial cells with a high proliferative index and primitive state was found to be significantly upregulated in MPM tumors and predictive of clinical outcomes. This subset also revealed new therapeutic vulnerabilities that could potentially be targeted to inhibit tumorigenesis.<br /><br />The study also investigated the tumor immune microenvironment of MPM. CD163 macrophages were predominantly distributed around the tumor islets, and CD8 T cells located closer to them were more terminally exhausted. This suggests that CD163 macrophages may play a role in driving immune exhaustion in MPM. Targeting CD163 macrophages along with anti-PD-1 therapy was found to enhance the efficacy of the treatment.<br /><br />Overall, this research sheds light on the cellular heterogeneity within the pleural mesothelium and provides a better understanding of MPM's pathobiology. It also identifies novel therapeutic targets and strategies to combat this challenging disease.

Asset Subtitle

Duo Xu

Meta Tag

Speaker Duo Xu

Topic Mesothelioma, Thymoma & Other Thoracic Tumors: Translational

Keywords

cellular heterogeneity

dysfunctional immunity

malignant pleural mesothelioma

single-cell transcriptome

pleural mesothelium

15 clusters

proliferative index

immune exhaustion

anti-PD-1 therapy

therapeutic targets