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Harnessing the Immune System

Ananda Goldrath, PhD
Chair, Molecular Biology Section
Division of Biological Sciences
Professor, UC San Diego Division of Biological Sciences


This project could help enhance the efficacy of existing immunotherapies and move discoveries to first-in-patient testing. Proven success may help ensure treatments target cancer cells efficiently and improve outcomes for patients. Funding for this project was generously provided by the Kimmelman Family.

The Need
Although cancer is a leading cause of death in the United States — and around the world — the human immune system holds enormous potential for preventing and controlling tumor formation. A better understanding of how cytotoxic T cells (CD8+ cells) develop anti-tumor qualities will enable researchers to accelerate more targeted treatment plans and identify novel therapies that capitalize on the immune system’s anti-tumor response.

The Opportunity
Most of our understanding of the way CD8+ cells function is based on observations of viral infection models in which CD8+ T cells differentiate into cytotoxic effector cells to target and eliminate infected host cells at the site of infection. These cells remain in the immune system, ready to respond to the pathogen more quickly and effectively in case of re- exposure. This model has been used to develop anti-cancer vaccines, but the recent discovery of a transcription factor that sustains immune cells that remain in specific tissues — tissue-resident memory cells (Trm) — may be used to help tumor-infiltrating lymphocytes (TIL) fight cancer cells.

Ananda Goldrath, PhD, is leading efforts to understand Trm cells, which could transform the way we think about cancer vaccines. These cells remain in non-lymphoid sites rather than circulating through blood and secondary lymphoid tissue, and function as a first line of defense against tumor regrowth in a number of tissues. Dr. Goldrath’s study investigates the ways TILs resemble Trm and how transcription factors influence these cells. Studies will observe the gene expression of Trm cells in different environments, test the capacity of CD8+ T cells influenced by transcription factors, and identify additional transcription factors that regulate Trm and TIL cells.

The Impact
This project could help enhance the efficacy of existing immunotherapies and move discoveries to first-in-patient testing. Proven success may help ensure treatments target cancer cells efficiently and improve outcomes for patients.