Sickle cell disease changes CD8+ T-cell chromatin structure, affecting cancer immunotherapy response.
Sickle cell disease altered CD8+ T-cell chromatin architecture, triggering ferroptosis and weakening antitumor immunity. Hydrogen sulfide treatment restored chromatin interactions and enhanced immune responses, improving immunotherapy effectiveness in renal medullary carcinoma.
Researchers analyzed CD8+ T cells from peripheral blood mononuclear cells of healthy donors and patients with SCD, examining chromatin architecture changes through Hi-C technology and DNA fluorescence in situ hybridization . Analysis included CD34+ hematopoietic stem cell–engrafted humanized mice with high human leukocyte engraftment showing over 75% human CD45+ leukocytes for RMC2C1 cell implantation studies. Treatment protocols involved administration of 10 mg/kg GYY4137 intraperitoneally twice weekly for 3 weeks, followed by anti–programmed cell death 1 antibody treatment at 200 μg per mouse twice weekly.CD8+ T cells from patients with SCD exhibited reduced SLC7A11 expression and increased lipid peroxidation compared with healthy control individuals, with a significantly decreased H2S concentration in serum samples biogenesis genes, thereby increasing susceptibility to ferroptosis. Therapeutic restoration of H2S concentration in SCD mice rescued SLC7A11 expression, mitigated ferroptosis, and enhanced immune and antitumor responses,” the authors of the study wrote.According to the authors, while Hi-C and DNA FISH analyses revealed chromatin interaction changes in CD8+ T cells under SCD conditions, altered T-cell subtypes and states may contribute to these findings. The researchers noted that while this study highlights SCD’s impact on ferroptosis and chromatin architecture, other tumor microenvironment–related factors remain to be examined. Additionally, the use of peripheral blood mononuclear cell–derived humanized mice may limit insights into early immune development and influence the robustness of tumor growth differences.This study was supported by grants from National Institutes of Health, Cancer Prevention and Research Institute of Texas, and Department of Defense. Pavlos Msaouel received funding from Gateway for Cancer Research, the Kidney Cancer Association, the V Foundation, and the MDACC Physician-Scientist Award. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.All material on this website is protected by copyright, Copyright © 1994-2025 by WebMD LLC. This website also contains material copyrighted by 3rd parties.
Biologics Sickle Cell Disease Sickle Cell Disease (SCD) Cancer Malignant Neoplasia Carcinoma Malignant Neoplasm Malignant Kidney Neoplasm Renal Cell Cancer Cancer Of The Kidney Renal Cell Carcinoma RCC Renal Cell Carcinoma (RCC) Genomics Genomic Medicine Kidney Cancer Renal Cancer Lysosomal Storage Disease Tumor I-Cell Disease Mucolipidosis Type Ii
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