Thaxton Lab | Research

Immune Cell Stress

Our laboratory studies the mechanisms through which immune cells in tumors experience tumor microenvironment (TME) stress. We have found that TME stressors such as hypoxia enforce ER stress proteins in T cells and macrophages in tumors promoting cellular dysfunction, such as T cell exhaustion.

We utilize Opal multiplex immunofluorescent imaging, spectral flow cytometry, metabolomics, Seahorse Bioanalysis, tumor mouse models and patient samples to study the chronic stress response in tumor immunity.

A mouse model with T cell-specific ATF4 gain of function with spectral flow cytometry indicates that ATF4 promotes loss of tumor control and exhaustion in CD8+ TILs.

ER stress transcription factor ATF4 is enforced in hypoxic tumor regions (PMO+). CD8+ T cells express high ATF4 when localized to hypoxic tumor regions.

Immune Cell Metabolism

Metabolism of tumor infiltrating T cells and tumor associated macrophages defines their antitumor capacity. We study how immune cell stress in the tumor microenvironment programs aberrant metabolism in CD8+ TILs and tumor associated macrophages to limit response to checkpoint therapies.

Confocal Imaging with complementary spectral flow cytometry identified that T cells isolated from tumors across multiple tumor microenvironments accrue lipid droplets.

Using a therapeutic currently in clinical trials, we found that remodeling lipid metabolism of CD8+ T cells enhanced antitumor immunity.

Immune Cell Structure

Organelle structure underlies healthy cellular function. We study the morphology of the endoplasmic reticulum and mitochondria in T cells and macrophages in the stress of the tumor microenvironment. We have used multiple innovative techniques to identify that the tumor microenvironment damages and dysregulates organelle structure in CD8+ T cells in tumors. We are studying strategies to modulate organelle structure in endogenous immunity and CAR-T cells to promote long-term antitumor immunity.