Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia

Sandén, Carl LU ; Landberg, Niklas LU orcid ; Peña-Martínez, Pablo LU ; Thorsson, Hanna LU ; Daga, Shruti LU ; Puente-Moncada, Noelia LU ; Rodriguez-Zabala, Maria LU ; von Palffy, Sofia LU ; Rissler, Marianne LU and Lazarevic, Vladimir LU orcid , et al. (2025) In Nature Cancer
Abstract

Immunotherapy has shown limited success in acute myeloid leukemia (AML), indicating an incomplete understanding of the underlying immunoregulatory mechanisms. Here we identify an immune evasion mechanism present in 60% of AML cases, wherein primitive AML cells aberrantly express the lymphoid surface protein SLAMF6 (signaling lymphocyte activation molecule family member 6). Knockout of SLAMF6 in AML cells enables T cell activation and highly efficient killing of leukemia cells in coculture systems, demonstrating that SLAMF6 protects AML cells from recognition and elimination by the immune system in a mode analogous to the programmed cell death protein-ligand (PDL1/PD1) axis. Targeting SLAMF6 with an antibody against the SLAMF6... (More)

Immunotherapy has shown limited success in acute myeloid leukemia (AML), indicating an incomplete understanding of the underlying immunoregulatory mechanisms. Here we identify an immune evasion mechanism present in 60% of AML cases, wherein primitive AML cells aberrantly express the lymphoid surface protein SLAMF6 (signaling lymphocyte activation molecule family member 6). Knockout of SLAMF6 in AML cells enables T cell activation and highly efficient killing of leukemia cells in coculture systems, demonstrating that SLAMF6 protects AML cells from recognition and elimination by the immune system in a mode analogous to the programmed cell death protein-ligand (PDL1/PD1) axis. Targeting SLAMF6 with an antibody against the SLAMF6 dimerization site inhibits the SLAMF6-SLAMF6 interaction and induces T cell activation and killing of AML cells both in vitro and in humanized in vivo models. In conclusion, we show that aberrant expression of SLAMF6 is a common and targetable immune escape mechanism that could pave the way for immunotherapy in AML.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Nature Cancer
publisher
Nature Publishing Group
external identifiers
  • scopus:105017873246
  • pmid:41044242
ISSN
2662-1347
DOI
10.1038/s43018-025-01054-6
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
2dd627ae-040a-4b28-a9d0-47438994aef8
date added to LUP
2025-10-06 08:42:43
date last changed
2025-11-29 04:01:13
@article{2dd627ae-040a-4b28-a9d0-47438994aef8,
  abstract     = {{<p>Immunotherapy has shown limited success in acute myeloid leukemia (AML), indicating an incomplete understanding of the underlying immunoregulatory mechanisms. Here we identify an immune evasion mechanism present in 60% of AML cases, wherein primitive AML cells aberrantly express the lymphoid surface protein SLAMF6 (signaling lymphocyte activation molecule family member 6). Knockout of SLAMF6 in AML cells enables T cell activation and highly efficient killing of leukemia cells in coculture systems, demonstrating that SLAMF6 protects AML cells from recognition and elimination by the immune system in a mode analogous to the programmed cell death protein-ligand (PDL1/PD1) axis. Targeting SLAMF6 with an antibody against the SLAMF6 dimerization site inhibits the SLAMF6-SLAMF6 interaction and induces T cell activation and killing of AML cells both in vitro and in humanized in vivo models. In conclusion, we show that aberrant expression of SLAMF6 is a common and targetable immune escape mechanism that could pave the way for immunotherapy in AML.</p>}},
  author       = {{Sandén, Carl and Landberg, Niklas and Peña-Martínez, Pablo and Thorsson, Hanna and Daga, Shruti and Puente-Moncada, Noelia and Rodriguez-Zabala, Maria and von Palffy, Sofia and Rissler, Marianne and Lazarevic, Vladimir and Juliusson, Gunnar and Ohlin, Mats and Hyrenius-Wittsten, Axel and Orsmark-Pietras, Christina and Lilljebjörn, Henrik and Ågerstam, Helena and Fioretos, Thoas}},
  issn         = {{2662-1347}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Cancer}},
  title        = {{Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia}},
  url          = {{http://dx.doi.org/10.1038/s43018-025-01054-6}},
  doi          = {{10.1038/s43018-025-01054-6}},
  year         = {{2025}},
}