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Deciphering Immune Complexity on the...

Kare, Aris John,

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Deciphering Immune Complexity on the Axes of Time & Space: High-Dimensional Profiling for Tissue Microenvironments /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Deciphering Immune Complexity on the Axes of Time & Space: High-Dimensional Profiling for Tissue Microenvironments // Aris John Kare.
Author:	Kare, Aris John,
Description:	1 electronic resource (232 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-03, Section: A.
Contained By:	Dissertations Abstracts International86-03A.
Subject:	Thymus gland. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31460320
ISBN:	9798384335504

Deciphering Immune Complexity on the Axes of Time & Space: High-Dimensional Profiling for Tissue Microenvironments /
Kare, Aris John,

Deciphering Immune Complexity on the Axes of Time & Space: High-Dimensional Profiling for Tissue Microenvironments /Aris John Kare. - 1 electronic resource (232 pages)

Source: Dissertations Abstracts International, Volume: 86-03, Section: A.

High-dimensional immunoprofiling on the axes of time, tissue, and treatment is necessary to unravel the heterogeneity within systems-wide responses to disease. We are witnessing a renaissance in the development of these methods, which have enabled greater parameterization, accuracy and throughput than previously achieved for studying systems immunology. The impact of T-cell targeted lipid nano particles (LNPs), a promising therapeutic strategy, was first assayed as a function of time and tissue using spectral cytometry. Reporter gene mRNA was packaged into CD3-targeted LNPs to transfect T cells in situ, and immune cells were assayed in the spleen, blood and tumors in the presence of immunotherapy. While promising transfection was achieved, an intense immune activation was associated with the anti-CD3 coating on the LNPs and created questions that required further dissection of immune cell subsets. These questions motivated an expansion of spectral cytometry techniques by engineering a 40-color deep immunophenotyping panel for murine lymphoid tissues and tumors. This tool was then applied to unlock mechanistic insights into combinatorial cancer immunotherapy, tissue leukocyte composition, and developmental trajectories in primary lymphoid tissues. While briefly highlighted herein, I use the majority of this thesis to discuss the engineering design principles behind a panel of this complexity, as such approaches have lacked comprehensive description in the existing literature. After achieving this high-resolution cellular phenotyping, the need to assay the spatial organization of immune and epithelial cells in cancers was apparent. With this focus in mind, a 51-plex CODEX assay was harmonized with Visium spatial transcriptomics to deconvolve the spatial architecture of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) microenvironments, as well as tertiary immune structure frequency and composition. This thesis concludes by leveraging the spatial transcriptomic assays to model microdosimetry patterns for several beta-emitting radionuclides, in order to inform future theragnostic development.

English

ISBN: 9798384335504Subjects--Topical Terms:

3827171
Thymus gland.

Deciphering Immune Complexity on the Axes of Time & Space: High-Dimensional Profiling for Tissue Microenvironments /
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520 $a High-dimensional immunoprofiling on the axes of time, tissue, and treatment is necessary to unravel the heterogeneity within systems-wide responses to disease. We are witnessing a renaissance in the development of these methods, which have enabled greater parameterization, accuracy and throughput than previously achieved for studying systems immunology. The impact of T-cell targeted lipid nano particles (LNPs), a promising therapeutic strategy, was first assayed as a function of time and tissue using spectral cytometry. Reporter gene mRNA was packaged into CD3-targeted LNPs to transfect T cells in situ, and immune cells were assayed in the spleen, blood and tumors in the presence of immunotherapy. While promising transfection was achieved, an intense immune activation was associated with the anti-CD3 coating on the LNPs and created questions that required further dissection of immune cell subsets. These questions motivated an expansion of spectral cytometry techniques by engineering a 40-color deep immunophenotyping panel for murine lymphoid tissues and tumors. This tool was then applied to unlock mechanistic insights into combinatorial cancer immunotherapy, tissue leukocyte composition, and developmental trajectories in primary lymphoid tissues. While briefly highlighted herein, I use the majority of this thesis to discuss the engineering design principles behind a panel of this complexity, as such approaches have lacked comprehensive description in the existing literature. After achieving this high-resolution cellular phenotyping, the need to assay the spatial organization of immune and epithelial cells in cancers was apparent. With this focus in mind, a 51-plex CODEX assay was harmonized with Visium spatial transcriptomics to deconvolve the spatial architecture of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) microenvironments, as well as tertiary immune structure frequency and composition. This thesis concludes by leveraging the spatial transcriptomic assays to model microdosimetry patterns for several beta-emitting radionuclides, in order to inform future theragnostic development.
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