Sickle cell disease changes DNA structure of cells to suppress immunity
MD Anderson Research Highlight May 12, 2025
Sickle cell disease changes DNA structure of cells to suppress immunity
Patients with sickle cell disease, an inherited disorder that affects red blood cells, have a higher risk of developing renal medullary carcinoma. This rare kidney cancer has a poor prognosis due to treatment resistance, but the underlying reasons for this are unknown. Therefore, researchers led by Pavlos Msaouel, M.D., Ph.D., Liuqing Yang, Ph.D., and Chunru Lin, Ph.D., examined the impact of sickle cell disease on immune function, cancer progression and treatment response. The results showed that sickle cell disease was associated with fewer CD8+ T cells in the spleen and lymph nodes as well as accelerated tumor growth in lab models of melanoma, breast cancer and kidney cancer. More specifically, sickle cell disease suppressed certain genes involved in ferroptosis, an iron-dependent cell death pathway, by changing the DNA structure of CD8+ T cells, which leads to lower hydrogen sulfide (H2S) production. Releasing H2S under certain conditions improved immune function in these models, suggesting a potential strategy to improve immunotherapy responses in these patients. Learn more in Immunity.
Our study uncovers a novel and unprecedented link between sulfur metabolism and immune function, showing that hydrogen sulfide is essential for maintaining cancer-fighting CD8+ T cells. This fundamental discovery changes how we understand immunity and opens new avenues for treating cancer in patients with sickle cell disease.