Raphaël Gottardo
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View article: Orchestrating Spatial Transcriptomics Analysis with Bioconductor
Orchestrating Spatial Transcriptomics Analysis with Bioconductor Open
Spatial transcriptomics technologies provide spatially-resolved measurements of gene expression through assays that can either target selected genes or capture transcriptome-wide expression profiles. The complexity and variability of these…
View article: 339 Engineered T cell therapy combined with PD-1, Lag-3 and Tim-3 checkpoint inhibition promotes pro-inflammatory CD4 T cell differentiation in an ovarian cancer mouse model
339 Engineered T cell therapy combined with PD-1, Lag-3 and Tim-3 checkpoint inhibition promotes pro-inflammatory CD4 T cell differentiation in an ovarian cancer mouse model Open
View article: 500 Biomarker identification of early response and resistance to combinatorial anti-angiogenic and immune-checkpoint blockade therapy in the recurrent ovarian cancer setting
500 Biomarker identification of early response and resistance to combinatorial anti-angiogenic and immune-checkpoint blockade therapy in the recurrent ovarian cancer setting Open
View article: 364 Systems immunology-guided <i>in vivo</i> CRISPR screens reveal a multifunctional E3 ligase that enhances adoptive T cell therapy for solid tumors
364 Systems immunology-guided <i>in vivo</i> CRISPR screens reveal a multifunctional E3 ligase that enhances adoptive T cell therapy for solid tumors Open
View article: Neuron-reactive KIR+CD8+ T cells display an encephalitogenic transcriptional program in autoimmune encephalitis
Neuron-reactive KIR+CD8+ T cells display an encephalitogenic transcriptional program in autoimmune encephalitis Open
View article: A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy
A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy Open
Adoptive T cell therapies have shown limited efficacy against solid tumors due in part to immunosuppressive cues such as from TGF-β and insufficient survival/proliferative signals within the tumor microenvironment (TME). We engineered chim…
View article: Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer
Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer Open
The five-year survival rate for ovarian cancer patients remains below 50%, underscoring the need for innovative therapies. One promising approach involves engineering T cells to specifically target proteins uniquely overexpressed in tumors…
View article: Bcl6 expression is associated with a distinct immune landscape and spatial transcriptome in COVID-19
Bcl6 expression is associated with a distinct immune landscape and spatial transcriptome in COVID-19 Open
The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the acute stages of viral infection, remains poorly understood. We have analyzed lung-draining lymph nodes (LD-LNs)…
View article: ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets
ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets Open
View article: Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering
Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering Open
Spatial omics technologies have revolutionized the study of tissue architecture and cellular heterogeneity by integrating molecular profiles with spatial localization. In spatially resolved transcriptomics, delineating higher-order anatomi…
View article: The Human Exersome Initiative (HEI): Rationale, study design, and protocol
The Human Exersome Initiative (HEI): Rationale, study design, and protocol Open
Habitual physical activity and exercise training (PA/EX) confers numerous health-benefits. Phenotypic adaptations and clinical health outcomes attributable to PA/EX are well-established, and molecular markers and mediators of the PA/EX res…
View article: A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence
A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence Open
Relapsed and/or refractory acute myeloid leukemia (AML) post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. We previously reported that post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8 + T cell…
View article: Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis
Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis Open
Given the role of follicular immune dynamics, especially the germinal centre, for the development of pathogen‐specific antibodies, their in situ characterisation is of great importance. We have developed a multiplex immunofluorescence imag…
View article: Transcriptome analysis of archived tumors by Visium, GeoMx DSP, and Chromium reveals patient heterogeneity
Transcriptome analysis of archived tumors by Visium, GeoMx DSP, and Chromium reveals patient heterogeneity Open
Recent advancements in probe-based, full-transcriptome technologies for FFPE tissues, such as Visium CytAssist, Chromium Flex, and GeoMx DSP, enable analysis of archival samples, facilitating the generation of data from extensive cohorts. …
View article: Unsupervised Clustering of Cell Populations in Germinal Centers Using Multiplexed Immunofluorescence
Unsupervised Clustering of Cell Populations in Germinal Centers Using Multiplexed Immunofluorescence Open
Follicles (Fs)/Germinal Centers (GCs) in tonsils and lymph nodes are dynamic microenvironments where diverse immune cell populations interact for the development of antibody responses against pathogens. The accurate in situ phenotypic anal…
View article: From Transcripts to Cells: Dissecting Sensitivity, Signal Contamination, and Specificity in Xenium Spatial Transcriptomics
From Transcripts to Cells: Dissecting Sensitivity, Signal Contamination, and Specificity in Xenium Spatial Transcriptomics Open
Spatial transcriptomics has transformed our ability to map gene expression within intact tissues at cellular and subcellular resolution. Among current platforms, Xenium is widely adopted for its reliability, accessibility, and high data qu…
View article: Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus
Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus Open
Introduction Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside of lymph node (LN) follicles. Methods Here,…
View article: <tt>tagtango</tt>: an application to compare single-cell annotations
tagtango: an application to compare single-cell annotations Open
Summary In this article, we present tagtango, an innovative R package and web application designed for robust and intuitive comparison of single-cell clusters and annotations. It offers an interactive platform that simplifies the explorati…
View article: Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases
Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases Open
View article: Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence
Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence Open
Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT i…
View article: Follicular Bcl6 reactivity is associated with a unique immune landscape and spatial transcriptome in COVID-19
Follicular Bcl6 reactivity is associated with a unique immune landscape and spatial transcriptome in COVID-19 Open
The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the early stages of viral infections, remains poorly understood. We have analyzed lung-draining lymph nodes (LD-LNs…
View article: Transcriptome Analysis of Archived Tumor Tissues by Visium, GeoMx DSP, and Chromium Methods Reveals Inter- and Intra-Patient Heterogeneity
Transcriptome Analysis of Archived Tumor Tissues by Visium, GeoMx DSP, and Chromium Methods Reveals Inter- and Intra-Patient Heterogeneity Open
Recent advancements in probe-based, full-transcriptome, high-resolution technologies for Formalin-Fixed Paraffin-Embedded (FFPE) tissues, such as Visium CytAssist, Chromium Flex (10X Genomics), and GeoMx DSP (Nanostring), have opened new o…
View article: Long term T cell response and safety of a tetravalent dengue vaccine in healthy children
Long term T cell response and safety of a tetravalent dengue vaccine in healthy children Open
View article: Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion
Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion Open
View article: ADTnorm: Robust Integration of Single-cell Protein Measurement across CITE-seq Datasets
ADTnorm: Robust Integration of Single-cell Protein Measurement across CITE-seq Datasets Open
CITE-seq enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADT…
View article: Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma
Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma Open
Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, wh…
View article: Supplementary Figures from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Supplementary Figures from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy Open
Figure S1. Cellular composition of the post-treatment tumor biopsy of patient UPN-03. Figure S2. Gating strategy for multiparameter flow cytometry for UPN-03. Figure S3. Gating strategy for multiparameter flow cytometry for UPN-04.
View article: Table S3 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Table S3 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy Open
Table S3. Cellular composition of post-infusion timepoints.
View article: Table S3 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Table S3 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy Open
Table S3. Cellular composition of post-infusion timepoints.
View article: Table S1 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Table S1 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy Open
Table S1. Baseline cytokine levels (prior to lymphodepletion) for UPN-03 and UPN-04.