Plasma cell heterogeneity and dynamics in patient tumors

ended

During the last decade, the ability to treat cancer by targeting the immune system has revolutionized cancer care, but many patients still fail to respond to current immunotherapies, which mainly target T cells. Besides T cells, the tumor microenvironment is home to many other immune cells; however, we are still unable to accurately predict and target the functions of most tumor-infiltrating immune cells, particularly in human cancer. These cells and their tumor-associated functions represent an untapped reservoir of therapeutic targets. Plasma cells (PC), which are antibody-producing cells derived from B cells, frequently infiltrate solid tumors and their presence associates with positive prognosis across cancer types; yet, our knowledge of tumor-infiltrating PC remains limited. The goal of this project is two-fold: first, I aim to use single cell RNA-seq coupled with spatial transcriptomics (developed by the host lab) to define the heterogeneity and spatial distribution of PC (and their subsets) relative to other cells/histological features in patient breast tumors. PC receptor expression and survival factors will be mapped to generate a PC-tumor stroma 'interactome', which should facilitate defining potential vantage points for therapy. Second, I aim to define the cellular age of tumor-infiltrating PC, since knowing how cells are replaced in a tissue could be highly relevant to both uncover fundamental cell turnover mechanisms and to define new therapeutic avenues. The combination of skillsets between the applicant (tumor immunology) and the host lab (spatial transcriptomics and carbon dating, the latter which uniquely can be used to determine cellular lifespan in humans) presents a unique opportunity for the feasibility and knowledge exchange involved in performing this work. This study’s results could help clarify fundamental questions regarding the biology of tumor-infiltrating plasma cells and help uncover novel anticancer therapeutic targets.