Pavlos Msaouel: SCD induces chromatin introversion and ferroptosis in CD8+ T cells to suppress anti-tumor immunity
Pavlos Msaouel, Assistant Professor of Genitourinary Medical Oncology at MD Anderson Cancer Center, shared a post on X about recent paper he and his colleagues authored:
“People living with sickle-cell disease (SCD) face high cancer risk, including Renal Medullary Carcinoma. Our latest Immunity study suggests a culprit is the reshaping CD8⁺ T cell chromatin by SCD.
Using Hi-C + multi-omics in mouse and humanised SCD models, we identified ‘chromatin introversion’: long-range contacts collapse, silencing anti-ferroptosis genes (including SLC7A11 and H₂S-biosynthesis enzymes).
As a result, CD8⁺ T cells become ferroptosis-prone in the tumour micro-environment weakening antitumor immunity and accelerating tumor growth of breast cancer, melanoma and Renal Medullary Carcinoma in SCD hosts.
Giving an H₂S donor restored SLC7A11 levels, rewired chromatin, blocked ferroptosis, rescued T-cell function and sensitized Renal Medullary Carcinoma tumors to immunotherapy. Proof-of-concept for precision immunotherapy in haemoglobinopathies.
Take-home:
Genetic disorders can reshape 3-D genome architecture of immune cells, tipping them into ferroptosis. Targeting the redox/ferroptosis axis may boost cancer immunity in SCD—and perhaps other settings.”
Title: Sickle cell disease induces chromatin introversion and ferroptosis in CD8+ T cells to suppress anti-tumor immunity
Journal: Immunity
Authors: Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Jun Yao, Lanxin Bei, Yaohua Zhang, Pengju Gong, Lisa A. Huang,Zhou Jiang, Jian Gao, Shuang Peng, Tina K. Nguyen, Menuka Karki, Bora Lim, Cassian Yee, Jared K. Burks, Qing Zhang, Li Ma, Jianjun Gao, Nizar M. Tannir, Leng Han, Dihua Yu, Linghua Wang, Michael A. Curran, Maria A. Gubbiotti, Giannicola Genovese, Boyi Gan, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin
Read Full Article.
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