Provoking the Immunotherapy Efficacy of Renal Medullary Carcinoma
Abstract
Renal medullary carcinoma (RMC) is a highly lethal cancer that predominantly affects young individuals of African descent with blood disorders such as sickle cell disease (SCD). Sickle cell disease causes a structural change in red blood cells, which causes them to take on a crescent-like shape. This change in red blood cells of the kidney tissue is linked to the incidence of RMC. Less than 5% of patients with RMC survive beyond 3 years. In order to prevent, diagnose, and treat this disease there is a need to develop strategies informed by a deeper understanding of its distinct molecular changes. Ferroptosis is a form of regulated cell death that is mediated by iron ion overload. In SCD, excess iron is released from the abnormal red blood cells and causes ferroptosis. Our findings found that immune T cells from both mice and human patients with SCD showed significant upregulation of ferroptosis markers compared to wild-type controls or healthy donors. We hypothesize that administration of hydrogen sulfide may enhance antitumor immunity by interacting with the free iron ions released by red blood cells and inhibiting ferroptosis. We therefore aim to (1) define that SCD promotes tumor growth of the RMC tumor, (2) determine whether ferroptosis induces immune T cell exhaustion in the setting of SCD, and (3) examine whether hydrogen sulfide administration of mice with SCD can sensitize RMC tumor to immunotherapy. Overall, the project will determine the linkage between SCD and RMC tumors, which will fill in current gaps of knowledge in the field of cancer biology. Additionally, we will provide a pioneering therapeutic strategy for treating SCD-related RMC in the clinical setting.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310132
Entities
People
- Zilong Zhao
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army