Session: 622. Lymphomas: Translational – Non-Genetic: Poster III
Hematology Disease Topics & Pathways:
Lymphomas, T Cell lymphoma, Diseases, Lymphoid Malignancies, Biological Processes, Molecular biology, Technology and Procedures, Omics technologies
Objectives: This study intends to progressively analyze the spatial characteristics of PTCL tumors and the inflammatory microenvironment at the genomic, cellular, and animal levels, using single-cell RNA sequencing combined with image mass cytometry and other multi-omics methods. On this basis, it focuses on the role and molecular mechanism of the Histamine-HRH2 axis in PTCL disease progression and drug resistance, verifying it at the cellular and animal levels. The project aims to fully explore potential therapeutic targets, providing new ideas for optimizing treatment schemes and overcoming drug resistance in PTCL patients.
Methods: By conducting single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we conducted a comprehensive investigation of the complexity of inflammatory microenvironmen in PTCL. We unveiled the role and molecular mechanism of the Histamine-HRH2 axis in the progression of PTCL as well as the potential drug resistance regulatory mechanisms. Immunohistochemistry, immunofluorescence, and publicly available microarray datasets were used to validate these findings.
Results: The present study highlighted histamine, an inflammatory mediator, was abundant in the microenvironment of PTCL and was associated with poor prognosis of patients. Histamine, upon interaction with the HRH2 receptor on tumor cell surfaces, triggers the secretion of CSF1, consequently inducing M2 macrophage polarization and mediates immune suppression. The expression of p-CREB and CEBPB were upregulated after the treatment of histamine, which mediated the transcriptional activation of CSF1. In addition, we uncovered that histamine and CSF1 played important roles in remodeling the tumor microenvironment of PTCL, and combination therapy with antihistamines and CSF1R inhibitors may effectively enhance tumor cell killing effect of HDAC inhibitor.
Conclusions: In this study, we constructed comprehensive single-cell atlas of PTCL tumors and inflammatory microenvironment, using single-cell RNA sequencing combined with image mass spectrometry. On this basis, for the first time, we elucidated the role and molecular mechanism of histamine/HRH2 receptor axis in the progression of PTCL, explored potential therapeutic targets to provide new strategies for optimizing clinical treatment of PTCL patients.
Disclosures: No relevant conflicts of interest to declare.
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