Research thoughts by:

Dennis Jones

Gordon Research Conference on lymphatics in Barga, Italy


I am grateful for the support of the Karin Grunebaum Cancer Research Foundation to fund the trip to Italy to present my laboratory's work on lymphatic metastasis at the Gordon Research Conference on Lymphatics. At the conference, I also lead a timely Power Hour discussion on promoting racial diversity in science.



Tumor-derived exosomes and T cell suppression


Immunotherapy to stimulate a patient’s immune system to attack cancer cells has been shown to be effective in eliminating metastatic cancer cells, a leading cause of mortality in cancer patients. However, most breast cancers respond poorly to T cell-directed immunotherapies. We have evidence that exosomes secreted from breast cancer tumors can attenuate T cell activation. While numerous studies have documented the effect of cancer cell-derived exosomes on the cytotoxic activity of T cells, our preliminary data from our new mouse breast cancer model show that exosomes from mesenchymal cells recruited to breast tumors exert strong suppressive effects on T cell activation. We therefore hypothesize that exosomes from the breast tumor microenvironment represent an additional barrier for the efficacy of cancer immunotherapies. However, cancer associated mesenchymal cell (CA-MC) exosomes are poorly characterized. During the award period, we will utilize proteomic profiling to gain novel insights into how CA-MC exosomes mediate T cell suppression. We will also use CRISPR-Cas9 to delete candidate genes in CA-MCs and then test the ability of the edited CA-MC exosomes to inhibit T cell activation. These studies will allow us to better understand how CA-MCs inhibit T cells and will form the basis for developing new strategies to reverse local and systemic T cell suppression mediated by tumor-derived exosomes.