Harnessing Immunotherapy Against Brain Cancer

John (Jack) Figg
Graduate Student, Biomedical Sciences Program, University of Florida College of Medicine

Brain cancer is the leading cause of cancer-related death in children. Despite intensive treatment, glioblastoma (GBM), the most aggressive glioma subtype, remains fatal. Immunotherapy has been proposed to resolve this medical need, but remains limited due to, in part, a high level of suppressive immune cells that aid in cancer growth. To address this, our lab has developed a new immunotherapy called adoptive cellular therapy (ACT) that uses hematopoietic stem cells and radiation. ACT increased survival life in multiple brain cancer models, but the exact mechanism by which ACT works to inhibit tumor growth is unknown. My preliminary data suggests that ACT significantly reduces the number of suppressive cells within brain tumors. Additionally, ACT significantly decreases a molecule known as CCL12, which acts as a ‘homing signal’ for suppressive cells to travel to brain tumors. Given this, we hypothesize that this loss of suppressive cells is related to decreased suppressive cell migration. Since this project’s inception, we have identified that a specific cell type known as a macrophage secretes CCL12 in the glioma microenvironment and that inhibition of macrophage-derived CCL12 blocks the ability of suppressive cells to migrate. Our future directions are focused on understanding the impact of skull-specific suppressive immune cells on gliomas. From this, we aim to better understand how reprogramming of the skull-specific immune cell niche with adoptive immunotherapies can overcome gliomas.

Jack Figg is an M.D./Ph.D. student in the Department of Neurosurgery in the University of Florida College of Medicine. He is being mentored by Dr. Catherine Flores, a tenured professor and principal investigator with the Preston A. Wells Jr. Center for Brain Tumor Therapy. Jack’s research focuses on unraveling the cellular mechanisms that underpin adoptive cellular therapy efficacy against high-grade gliomas.


Core Standards

SC.912.L.16.8 Explain the relationship between mutation, cell cycle, and uncontrolled cell growth potentially resulting in cancer.

SC.912.L.16.10 Evaluate the impact of biotechnology on the individual, society and the environment, including medical and ethical issues

SC.912.N.4.2 Weigh the merits of alternative strategies for solving a specific societal problem by comparing a number of different costs and benefits, such as human, economic, and environmental.

SC.912.N.1.6 Describe how scientific inferences are drawn from scientific observations and provide examples from the content being studied.

SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and pathogenic agents to health from the perspectives of both individual and public health.

SC.912.L.14.52 Explain the basic functions of the human immune system, including specific and nonspecific immune response, vaccines, and antibiotics.

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