Date of Completion

Spring 5-1-2026

Thesis Advisor(s)

Kevin P. Claffey; Joseph J. LoTurco

Honors Major

Physiology and Neurobiology

Abstract

Sentinel lymph nodes are the first nodes that receive drainage from a tumor and are commonly used to evaluate whether cancer has begun to spread, but they also provide an important window into how a patient’s immune system is reacting to tumor-derived antigens. This project examines immune activity within SLNs, with particular attention to germinal centers, where B cells mature, undergo clonal expansion and somatic hypermutation, and generate improved antibody responses. Using a combination of spatially mapped immune marker staining, rapid sampling of reactive germinal centers, cytokine profiling, and single-cell/single-nucleus RNA sequencing, the study aims to characterize the localization, activation states, and phenotypes of B and T cells and to define the local immune environment within individual sentinel nodes. A central goal is to identify tumor-reactive B-cell receptor sequences from expanded and hypermutated B-cell clones and use these data to generate recombinant antibodies for functional testing against breast cancer cell lines, patient-derived tumor models, and archived patient tumor tissues. Antibodies that show selective binding are further evaluated across breast and pan-cancer tissue arrays to assess target distribution and specificity. Overall, this research seeks to provide a clearer and more comprehensive understanding of antigen-driven immune responses in patient-derived sentinel lymph nodes while creating a pathway for the discovery of clinically relevant tumor-targeting antibodies that may support future diagnostic and therapeutic applications. As part of this effort, I contribute to Dr. Claffey’s ongoing research by supporting the analysis of SLN immune responses and tumor-associated antigen reactivity in breast cancer.

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