William H. Hudson, PhD, Technology Impact Award Grantee

Dr. William H. Hudson is adapting T cell receptor (TCR) sequencing technology for use on preserved tissue samples to improve our understanding of how TCR specificity affects T cell function within the tumor microenvironment as well as cancer progression.

T cells are a critical arm of the adaptive immune system, capable of recognizing non-self-protein fragments known as neo-antigens that are presented by infected and cancerous cells. Immunotherapies that enhance T cell responses, such as checkpoint inhibitors, have had a profound effect on the treatment of many cancers. In addition to dictating what neo-antigen a T cell will target, the T cell receptor provides a natural “barcode” that can be used to track T cell clones in the body over time. If two T cells share the same TCR, they are clonally related and have identical target specificity, allowing powerful inferences about their function and available differentiation pathways.

Recently, Dr. Hudson adapted TCR sequencing, which allows comparison of T cell specificity between multiple samples, to spatial transcriptomics, allowing him to characterize specific T cell clones and where they’re located within the tumor microenvironment.

However, this adaptation relied on the use of fresh-frozen tissue, preventing its use on “fixed” or preserved tissue, which is widely available for thousands of patients. The goal of Dr. Hudson’s project is to adapt spatial TCR-sequencing to preserved tissue to allow for more in depth analysis of T cells, especially their activity and location within tumors.

By widening the availability of this powerful technique, banked human tumor samples can be used to understand the type and distribution of T cell clones within the tumor microenvironment and their relationship to disease progression and response to immunotherapy.

Projects and Grants
Adapting spatial T cell receptor sequencing to FFPE tissue

Baylor College of Medicine | All Cancers | 2023