자료유형  

 학위논문

Control Number  

0017162962

International Standard Book Number  

9798384335504

Dewey Decimal Classification Number  

611.4

Main Entry-Personal Name  

Kare, Aris John.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

232 p.

General Note  

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

General Note  

Advisor: Ferrara, Katherine.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2024.

Summary, Etc.  

요약High-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.

Subject Added Entry-Topical Term  

Thymus gland.

Subject Added Entry-Topical Term  

Cancer.

Subject Added Entry-Topical Term  

Lymphocytes.

Subject Added Entry-Topical Term  

Spleen.

Subject Added Entry-Topical Term  

Pharmacokinetics.

Subject Added Entry-Topical Term  

Flow cytometry.

Subject Added Entry-Topical Term  

Dendritic cells.

Subject Added Entry-Topical Term  

Immunotherapy.

Subject Added Entry-Topical Term  

Lasers.

Subject Added Entry-Topical Term  

Cytokines.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Optics.

Subject Added Entry-Topical Term  

Pharmacology.

Subject Added Entry-Topical Term  

Therapy.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-03A.

Electronic Location and Access  

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Control Number  

joongbu:657327