Date of Completion

2021

Thesis Type

College of Arts and Science Honors

Department

Medicine (Immunobiology)

First Advisor

Dr. Ralph Budd

Second Advisor

Dr. Rory Waterman

Third Advisor

Dr. Jonathan Boyson

Keywords

Immunology, Medicine, Immunobiology, Non-Small Cell Lung Cancer, Immune Cell Cancer Therapy, Cisplatinum

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in people in the United States.1Once the cancer has metastasized (stage IV), the five-year overall survival rate decreases to less than 5%.2 Numerous efforts have been conducted to find new forms of therapy that target these tumor cells. Gamma delta (gd) T cells and CD8+ T cells manifest robust cytolytic machinery to kill cancerous or virally infected cells. Tumor cells and other immune cells can inhibit T cell effector function by expressing PD-L1 (Programmed Death-Ligand 1) that engages PD-1 on chronically activated T cells.3 In the current study, NSCLC tumor aspirations from six patients undergoing intralesional cisplatinum chemotherapy were examined using multi-color flow cytometry to define the composition of immune cells, their state of activation, and their expression of PD-1 and PD-L1. We observed that, compared to peripheral blood mononuclear cells, the tumor infiltrating immune cells manifested elevated numbers of activated T cells expressing CD25 and CD56, and increased proportions of CD8+ and gd T cells. These studies demonstrate the feasibility of identifying and phenotyping tumor-infiltrating immune cells using intralesional aspiration and set the stage for future studies using single cell RNAseq and to potentially develop cell-based immune therapy.

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