Macrophages and fibroblasts in the progression of lung cancer

Stanford University, Stanford CA

Investigators

Abstract

Lung cancer is the leading cause of death in the United States, with over 125,000 patients predicted to die of lung cancer in 2024. Despite improvements to treatments, such as advancements in immune therapy, patients diagnosed at late-stage diseases have low response rates to therapies across the board. Aside from immunotherapies, there are few therapies that target the stromal components within the tumor microenvironment. Macrophages and fibroblasts have been shown to be some of the most abundant stromal cell types in tumors and have been found to contribute to immune suppression in the tumor microenvironment. To better understand how macrophages and fibroblasts contribute to immune suppression, In Aim 1, I will adapt CRISPR/Cas9 mediated gene editing to inactivate ~50 genes in macrophages in vivo and track macrophage phenotypes throughout lung cancer tumor progression. In Aim 2 I will inactivate ~50 genes in fibroblasts in vivo, tracking phenotypes and identifying important pathways in fibroblast that drive tumor progression. In Aim 3 I will determine how our top candidate genes in macrophages and fibroblast impact the large tumor microenvironment and functionally determine how they contribute to immune suppression. This study will elucidate stromal cell phenotypes of importance at various stages of tumor progression and has the potential to reveal new stromal targets to improve immunotherapies in lung cancer.