Studying immune cells that fight cancer

The body contains naturally occurring immune cells known as CD8+ T cells that serve as a cancer surveillance system. The cells have the capacity to identify and kill off malignant cells. The problem is that CD8+ T cells become depleted of energy and, in their "tired" state, lose the ability to destroy the cancer. My thesis work asked whether it may be possible to enhance the energy of CD8+ T cells by increasing their internal energy source, known as mitochondrial ATP, while limiting the production of a toxic byproduct of metabolism that can further damage cells.

In my research, I used RNA sequencing and identified a key enzyme that plays a role in CD8+ T-cell metabolism. The enzyme is malic enzyme 1, or ME1. I then used mRNA transfection technology, which inserts protein-producing messenger RNA into cells, aiming to increase the levels of ME1 in human CD8+ T cells. Our team found that we were able to increase the availability of mitochondrial ATP, providing additional energy to CD8+ T cells. We were also able to increase their killing capacity without the accumulation of toxic molecules, known as reactive oxygen species, that induce cellular exhaustion.

Importantly, we showed that ME1 increases the killing capacity of immune cells from patients with advanced cancers who have not responded to standard therapies. For patients with advanced disease and limited treatment options, ME1 may have a therapeutic use on its own or in a combination therapy. Our work has been accepted for publication in the journal Science Advances.