ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells
Abstract
Introduction: Acyl CoA binding protein (ACBP, encoded by the gene diazepam binding inhibitor, DBI) is a tissue stress hormone involved in pathological aging that mediates immunosuppression. The antibody-mediated neutralization of ACBP/DBI enhances anticancer immune responses in the context of chemoimmunotherapy. ACBP/DBI inhibition also upregulates the expression of the anti-aging gene Lmna coding for Lamin A in tumor-infiltrating T lymphocytes. This study was designed to explore the role of Lmna in the anticancer effects of ACBP/DBI neutralization. Methods: We generated mice lacking Lmna expression in T lymphocytes due to a conditional knockout. Mice bearing orthotopic (cutaneous) MCA205 fibrosarcomas were treated with an anti-ACBP/DBI monoclonal antibody in the context of chemoimmuntherapy (oxaliplatin combined with a PD-1 blocking antibody), and tumor growth was monitored. Results: As compared to immunocompetent control mice, in which ACBP/DBI neutralization plus chemoimmunotherapy was highly efficient in reducing MCA205 growth, mice lacking ACBP/DBI in T cells largely failed to respond to the therapeutic intervention. This result was undistinguishably observed in both female and male mice. Discussion: Altogether, these results indicate that Lmna expression by T lymphocytes is required for the anticancer effects of the combination of chemoimmunotherapy and ACBP/DBI neutralization. We conclude that lamin A, a factor required for optimal T cell activation, is causally involved in the immunostimulatory effects of ACBP/DBI neutralization.
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BibTeX
@article{li2026acbpdbi,
title = {{ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells}},
author = {Sijing Li and Carlos López-Otín and Maria Chiara Maiuri and Isabelle Martins and Guido Kroemer},
journal = {ImmunoTargets and Therapy},
year = {2026},
month = sep,
doi = {10.2147/itt.s604318},
url = {https://hal.science/hal-05801081v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells
AU - Sijing Li
AU - Carlos López-Otín
AU - Maria Chiara Maiuri
AU - Isabelle Martins
AU - Guido Kroemer
PY - 2026
DA - 2026/09/18
JO - ImmunoTargets and Therapy
DO - 10.2147/itt.s604318
UR - https://hal.science/hal-05801081v1
AB - Introduction: Acyl CoA binding protein (ACBP, encoded by the gene diazepam binding inhibitor, DBI) is a tissue stress hormone involved in pathological aging that mediates immunosuppression. The antibody-mediated neutralization of ACBP/DBI enhances anticancer immune responses in the context of chemoimmunotherapy. ACBP/DBI inhibition also upregulates the expression of the anti-aging gene Lmna coding for Lamin A in tumor-infiltrating T lymphocytes. This study was designed to explore the role of Lmna in the anticancer effects of ACBP/DBI neutralization. Methods: We generated mice lacking Lmna expression in T lymphocytes due to a conditional knockout. Mice bearing orthotopic (cutaneous) MCA205 fibrosarcomas were treated with an anti-ACBP/DBI monoclonal antibody in the context of chemoimmuntherapy (oxaliplatin combined with a PD-1 blocking antibody), and tumor growth was monitored. Results: As compared to immunocompetent control mice, in which ACBP/DBI neutralization plus chemoimmunotherapy was highly efficient in reducing MCA205 growth, mice lacking ACBP/DBI in T cells largely failed to respond to the therapeutic intervention. This result was undistinguishably observed in both female and male mice. Discussion: Altogether, these results indicate that Lmna expression by T lymphocytes is required for the anticancer effects of the combination of chemoimmunotherapy and ACBP/DBI neutralization. We conclude that lamin A, a factor required for optimal T cell activation, is causally involved in the immunostimulatory effects of ACBP/DBI neutralization.
SN - 2253-1556
ER -