Moshe Sade-Feldman
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View article: Lymphotoxin-driven cancer cell eradication by tumoricidal CD8 <sup>+</sup> TIL
Lymphotoxin-driven cancer cell eradication by tumoricidal CD8 <sup>+</sup> TIL Open
Tumor-infiltrating lymphocyte (TIL) therapy is FDA-approved for patients with treatment-resistant advanced melanoma, but the TIL subpopulations critical for tumor eradication remains incompletely understood. Using patient-derived TIL-melan…
View article: 498 Integrated scRNAseq, TCR repertoire and spatial transcriptomic analysis reveals immune remodeling induced by combined BRAF/MEK/PD-1 inhibition in metastatic BRAFV600E colorectal cancer
498 Integrated scRNAseq, TCR repertoire and spatial transcriptomic analysis reveals immune remodeling induced by combined BRAF/MEK/PD-1 inhibition in metastatic BRAFV600E colorectal cancer Open
View article: 371 Lymphotoxin-driven cancer cell eradication by tumoricidal CD8+ TIL
371 Lymphotoxin-driven cancer cell eradication by tumoricidal CD8+ TIL Open
View article: A multimodal atlas of COVID-19 severity identifies hallmarks of dysregulated immunity
A multimodal atlas of COVID-19 severity identifies hallmarks of dysregulated immunity Open
The alpha-variant wave of the COVID-19 pandemic provided a unique opportunity to study, at single-cell resolution, how near-universal exposure to the same pathogen can lead to either effective or dysfunctional immune responses in humans. A…
View article: RNA splicing dynamics in CD8 T cells uncovers isoforms that impact T cell-mediated cancer immunotherapy
RNA splicing dynamics in CD8 T cells uncovers isoforms that impact T cell-mediated cancer immunotherapy Open
Immune checkpoint blockade has transformed cancer therapy, yet many patients fail to respond, and few new targets have emerged beyond PD-1 and CTLA-4. Alternative splicing dramatically diversifies the T cell proteome, but the functional ro…
View article: Specific oncogene activation of the cell of origin in mucosal melanoma
Specific oncogene activation of the cell of origin in mucosal melanoma Open
Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we develop a zebrafish model in which all melanocytes experience CCND1 expression and loss of PTEN and TP53. Surprisingly, …
View article: CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors
CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors Open
The mitotic inhibitor docetaxel (DTX) is often used to treat endocrine-refractory metastatic breast cancer, but initial responses are mitigated as patients develop disease progression. Using a cohort of ex vivo cultured circulating tumor c…
View article: Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants
Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants Open
View article: CREB5 promotes immunotherapy resistance via tumor-intrinsic collagen matrix deposition
CREB5 promotes immunotherapy resistance via tumor-intrinsic collagen matrix deposition Open
Treatment with immune checkpoint inhibitors induces remarkable clinical responses in several cancer types. However, most cancer patients fail to respond to immunotherapy, and patients who initially respond often exhibit acquired resistance…
View article: Multimodal blood based profiling reveals insights into mechanisms of immunotherapy resistance
Multimodal blood based profiling reveals insights into mechanisms of immunotherapy resistance Open
Many cancer patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Circulating biomarkers have the potential to identify patients with primary resistance or early progression on therapy to alter tre…
View article: Unveiling alternative splicing dynamics in activated T lymphocytes and their implications for immune checkpoint blockade efficacy
Unveiling alternative splicing dynamics in activated T lymphocytes and their implications for immune checkpoint blockade efficacy Open
Alternative splicing (AS) generates diverse mRNA transcripts from a single gene, enhancing protein variety. This study examines AS during naive CD4 T cell activation, revealing that splicing events precede gene expression changes, evident …
View article: Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma
Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma Open
Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The combined positive score (CPS) for PD-L1 is the only biomarker approved to predic…
View article: First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer
First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer Open
NCT04290546.
View article: Figure S9 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S9 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S9 | Supporting data for single cell RNA sequencing of CAR-T in 3D co-cultures with PDOTS.
View article: Figure S8 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S8 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S8 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.
View article: Figure S1 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S1 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplementary Figure S1 | Supporting data demonstrating B7-H3 expression in melanoma and other cancers.
View article: Table S1 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Table S1 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
PDOTS patient data (accompanying Fig. 1)
View article: Data from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Data from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell ther…
View article: Table S3 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Table S3 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
PDOTS patient data (accompanying Fig. 3)
View article: Figure S7 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S7 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S7 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.
View article: Figure S4 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S4 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S4 | Supporting data for ex vivo profiling of PD-1 blockade and TBK1 inhibition in combination with B7-H3.CAR-T cells using PDOTS.
View article: Figure S11 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S11 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S11 | Supporting data that targeting TBK1 sensitizes cancer cells to CAR-T cell-derived TNFα/IFNγ.
View article: Figure S6 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S6 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S6 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.
View article: Figure S10 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S10 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S10 | Supporting data for single cell RNA sequencing of native tumor-infiltrating lymphocytes following CAR-T challenge in 3D co-cultures with PDOTS.
View article: Figure S2 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S2 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplementary Figure S2 | Supporting data for the In vitro characterization and efficacy of B7-H3.CAR-T cells.
View article: Figure S3 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S3 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S3 | Supporting data for ex vivo profiling of B7-H3.CAR-T cells using PDOTS.
View article: Table S2 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Table S2 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
PDOTS patient data (accompanying Fig. 2)
View article: Figure S5 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Figure S5 from TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Supplemental Figure S5 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.
View article: TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids Open
Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell ther…
View article: Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade
Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade Open
The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted in various preclinical investigations, yet the mechanism of action in humans remains unknown. To decipher the combi…