Biology subjects

Reiss, Y.

Publications and source records attributed to Reiss, Y..

4 recordsLinked to original sources

bioRxiv2025

Benchmarking cell-type deconvolution in cross-platform transcriptomic data

BackgroundTranscriptomic data from diverse measurement technologies are widely used to study tissue heterogeneity. Cell-type deconvolution, which resolves mixed transcriptomic signals into cellular components, is a key analytical approach. However, achieving accurate deconvolution across platforms remains challenging due to platform-specific experimental and technological biases. ResultsWe systematically benchmarked deconvolution performance using real-world cross-platform datasets and simulated data modeling distinct technological features. Our analyses provide practical guidelines for experimental design and promote more robust and comparable cross-platform transcriptomic analyses. ConclusionLog-normal regression methods such as SpatialDecon demonstrated the most reliable and consistent performance across both simulated and experimental settings, establishing a robust framework for accurate cross-platform transcriptomic deconvolution. Moreover, our results highlight potential caveats in deconvolution predictions arising from specific experimental conditions, providing guidance for more informed experimental design and interpretation Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/690141v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@585cbdorg.highwire.dtl.DTLVardef@13088c7org.highwire.dtl.DTLVardef@163ea75org.highwire.dtl.DTLVardef@b5ccf7_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Modulation of the ATP-adenosine signaling axis combined with radiotherapy facilitates anti-cancer immunity in brain metastasis

The immunosuppressive microenvironment in the brain poses a major limitation to successful therapy for brain metastases. Here we report that blockade of the ATP-to-adenosine-converting enzymes CD39 and CD73 and the adenosine receptor A2AR in combination with radiotherapy attenuates tumor progression in a breast-to-brain metastasis model by facilitating anti-cancer immunity. Immunophenotyping revealed loss of exhausted T cells and higher abundance of anti-cancer effector T cell populations. This effect was accompanied by a decrease of immunosuppressive lipid-laden macrophages and an expansion of CD14CD33high macrophages associated with antigen presentation. Analyses of human brain metastases samples supports a role of the ATP-adenosine signaling axis in modulating tumor inflammation and identified expression of CD39 and adenosine deaminase as predictive markers for patient survival and/or immune infiltration. Our findings demonstrate that the adenosine axis represents a druggable pathway to achieve local immunomodulation and treatment response, opening a new therapeutic avenue for brain metastases patients.

cancer biology↗

bioRxiv2024

Identification and characterization of tertiary lymphoid structures in brain metastases

Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM, mostly from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was more common in treatment-naive BrM and associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.

cancer biology↗

bioRxiv2024

Glioma-associated tertiary lymphoid structures are sites of lymphocyte clonal expansion and plasma cell formation

Adult-type diffuse gliomas, the most common primary brain tumors, pose significant clinical challenges due to limited treatment options, restricted anti-tumor immune response and dismal patient prognosis. In this study, we elucidate the immunological function and clinical relevance of intra-tumoral tertiary lymphoid structures (TLS) in adaptive anti-glioma immunity. We conducted a comprehensive, unbiased analysis of lymphoid aggregation in 642 gliomas using a multi-modal approach that combines RNA sequencing with spatial transcriptome and proteome profiling. Our findings reveal that TLS are present in 15% of tumors and correlate with improved overall survival. Gliomas with TLS exhibit a remodeled perivascular space, marked by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Furthermore, we demonstrate that TLS maturation into sites of dynamic adaptive immune responses, characterized by clonal T and B cell expansion and IgA+ and IgG+ plasma-cell formation, is driven by efficient early T cell recruitment to the perivascular space.

immunology↗