Data from SOCS1 Protects Acute Myeloid Leukemia against Allogeneic T Cell–Mediated Cytotoxicity
Year: 2025
Type: other
Abstract: Despite the curative potential of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML), its efficacy is limited by intrinsic resistance of cancer cells to donor-derived T-cell cytotoxicity. Using a genome-wide CRISPR screen, we identified the SOCS1–JAK1–STAT1 pathway as a mediator of AML susceptibility to T cells. Knockdown of SOCS1 in AML cells sensitized them to killing by allogeneic T cells, whereas SOCS1 overexpression in AML cells induced resistance to T-cell antileukemic activity. Mechanistically, SOCS1 protected AML cells from T-cell killing by antagonizing IFNγ–JAK1—induced ICAM-1 expression. Furthermore, primary AML cells with lower SOCS1 expression correlated with better overall survival in patients, especially those with a lower exhausted CD8+ T-cell score. Thus, this study reveals SOCS1 and its downstream mediators as a potential targetable pathway to enhance T cell–based immunotherapy for AML. Significance: Our investigation of the SOCS1 pathway in AML and T-cell interactions provides insights into potential mechanisms of resistance of AML to allogeneic hematopoietic stem cell transplantation and demonstrates the potential of targeting SOCS1 and its downstream mediators to enhance antileukemic T-cell activity. See related commentary by Fry, p. 157.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410099883