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Terasaki Talks: Dr. Karim Mahiddine

"The Role of Tumor Hypoxia in the Immune Response to Solid Tumors"

Abstract:

Tumor hypoxia is thought to promote the recruitment and T-cell suppressive activity of polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs). However, the net effect of hypoxia on PMNs within the overall context of the tumor microenvironment remains incompletely understood. To address this issue, we administered in vivo respiratory hyperoxia as a novel way to alleviate tumor hypoxia. Applying this approach to a clinically relevant model of endometrial cancer revealed tumor hypoxia as a potent inhibitor of anti-tumor PMN function. Moreover, hypoxia relief dramatically reduced uterine tumor burden in a PMN-dependent, but T cell-independent fashion. In addition to revealing novel aspects of direct PMN effector mechanisms in cancer, I will also discuss my futures directions that support the emerging possibility that relief of hypoxia is an attractive adjunct modality in cancer immunotherapy.

Biography:

Dr. Mahiddine completed his postdoctoral training in at the French National Institute of Health and Medical Research in Toulouse, France. He studied how the thymus specific serine protease controlled the development of thymocytes in the context of autoimmune diseases. He joined the Department of Laboratory Medicine at the University of California San Francisco in 2016, as a senior scientist, and his interest lies in understanding how tumor hypoxia compromises innate and adaptive immune cells, to ultimately promote tumor progression.

Dr Mahiddine developed the use of respiratory hyperoxia (60% oxygen) to alleviate tumor hypoxia, thus establishing a method to study the effects of hypoxia on the immune response towards cancer, including the metastatic process. Besides giving basic insight into the role of neutrophils in cancer, which has remained largely obscure, Dr. Mahiddine investigations are aimed to determine whether relief from tumor hypoxia, either through the administration of respiratory hyperoxia or hypoxia-targeting small molecules, could ultimately be used an adjunct modality of cancer immunotherapy, especially in cases where T cell-based immunotherapies (e.g. “checkpoint blockade”) have failed.

Event Information

Event Date 07-15-2020 8:00 am
Event End Date 07-15-2020
Registration Start Date 06-28-2020
Cut off date 07-15-2020 8:15 am

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