Publications by authors named "Samuel Markson"
Article Synopsis
- In vivo T cell screens are essential for understanding immunity, but there's currently no agreed-upon design for their implementation, including factors like gene library size, the amount of cells transferred, and the number of mice used in experiments.
- The Framework for In vivo T cell Screens (FITS) is introduced to standardize these parameters, ensuring robust and effective experimental outcomes across various contexts.
- As a practical application, the researchers used FITS to enhance a CD8+ T cell screen in a tumor model, incorporating unique molecular identifiers (UMIs) to boost statistical analysis and monitor T cell behavior linked to different gene knockouts.
Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment; however, only a subset of patients with brain metastasis (BM) respond to ICI. Activating mutations in the mitogen-activated protein kinase signaling pathway are frequent in BM. The objective of this study was to evaluate whether therapeutic inhibition of extracellular signal-regulated kinase (ERK) can improve the efficacy of ICI for BM.
View Article and Find Full Text PDFAnnotation of immunologic gene function in vivo typically requires the generation of knockout mice, which is time consuming and low throughput. We previously developed CHimeric IMmune Editing (CHIME), a CRISPR-Cas9 bone marrow delivery system for constitutive, ubiquitous deletion of single genes. Here we describe X-CHIME, four new CHIME-based systems for modular and rapid interrogation of gene function combinatorially (C-CHIME), inducibly (I-CHIME), lineage-specifically (L-CHIME) or sequentially (S-CHIME).
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- Immune-related adverse events (irAEs) can occur during PD-1 cancer immunotherapy and need more research to understand how they compare to regular autoimmune diseases.
- A study using single-cell RNA sequencing on mice showed that anti-PD-1 therapy caused distinct changes in T cells associated with type 1 diabetes (T1D), leading to differences in cell types and function compared to naturally occurring T1D.
- Findings suggest that blood samples from mice treated with anti-PD-1 can be valuable for monitoring irAEs, as the T cell markers differ from those seen in spontaneous T1D, providing potential insights for patient treatment.
In a recent article, Puig-Saus et al. computationally predict and experimentally validate neoantigen-specific T cell responses in patients with melanoma. They identify a restricted set of neoantigens recognized by polyclonal CD8 T cells as a unique feature of anti-PD-1 responders and engineer autologous tumor-responsive T cells expressing neoantigen-specific TCRs, providing proof-of-concept for future cellular therapies.
View Article and Find Full Text PDFMelanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions.
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- * We conducted two clinical trials to study the effectiveness of immune checkpoint inhibitors (ICI) in treating LMD and analyzed patient samples using advanced techniques like single-cell RNA sequencing.
- * Our research reveals important insights into the tumor environment in LMD and demonstrates the potential of using genomic profiling to enhance understanding and treatment strategies for this condition.
Article Synopsis
- Leptomeningeal disease (LMD) is a severe cancer complication often missed due to the low accuracy of current diagnostic methods like CSF cytology.
- This study aimed to evaluate if analyzing cell-free DNA (cfDNA) in CSF could provide a more reliable diagnosis for LMD compared to traditional cytologic methods.
- In a cohort of 30 patients, cfDNA analysis identified LMD correctly in 94% of follow-up samples, significantly outperforming cytologic analysis, indicating a potential improvement in diagnosing LMD.
We calculate vibrational spectra of ultralong-range Cs(32p) Rydberg molecules that form in an ultracold gas of Cs atoms. We account for the partial-wave scattering of the Rydberg electrons from the Cs perturber atoms by including the full set of spin-resolved S and P scattering phase shifts, and allow for the mixing of singlet (S=0) and triplet (S=1) spin states through Rydberg electron spin-orbit and ground state electron hyperfine interactions. Excellent agreement with observed data in Saßmannshausen et al.
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