SOCS1 protects acute myeloid leukemia against allogeneic T cell-mediated cytotoxicity

Tin, E, Rutella, S ORCID: https://orcid.org/0000-0003-1970-7375, Khatri, I, Na, Y, Yan, Y, MacLean, N, Vadakekolathu, J ORCID: https://orcid.org/0000-0002-2671-4285, Minden, MD, Schimmer, AD, Lee, J and Zhang, L, 2025. SOCS1 protects acute myeloid leukemia against allogeneic T cell-mediated cytotoxicity. Blood Cancer Discovery. ISSN 2643-3230

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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. SOCS1 knockdown in AML cells sensitized them to killing by allogeneic T cells, whereas SOCS1 overexpression in AML cells induced resistance to T-cell anti-leukemic 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.

Item Type:	Journal article
Publication Title:	Blood Cancer Discovery
Creators:	Tin, E., Rutella, S., Khatri, I., Na, Y., Yan, Y., MacLean, N., Vadakekolathu, J., Minden, M.D., Schimmer, A.D., Lee, J. and Zhang, L.
Publisher:	American Association for Cancer Research
Date:	10 February 2025
ISSN:	2643-3230
Identifiers:	Number Type 10.1158/2643-3230.bcd-24-0140 DOI 2378251 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	18 Feb 2025 13:21
Last Modified:	18 Feb 2025 13:21
URI:	https://irep.ntu.ac.uk/id/eprint/53059

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