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ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells

Year: 2026
Type: article
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. Keywords: endozepine, Hutchinson-Gilford progeroid syndrome, immune checkpoint inhibitor, immunotherapy, progeria
DOI: 10.2147/itt.s604318
Institutions: Inserm, Université Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, University of Naples Federico II, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,320
Funders: Seerave Foundation, Equipex, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Institut National Du Cancer, Direction Générale de l’offre de Soins
Awards: G1190173965, G1348591106, G1397743473, G1540355574, G1743485262, G1912211089, G1941370527, G2109069054, G2179318311, Lung cancer prevention and interception, Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception., G2351262490, G2469459663, G2485135851, Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response., G2699422577, G2714391379, G3116448791, G3231222199, Mitochondrial copper targeting to modulate inflammatory macrophages, G3489513111, G3745988485, G4364925233, G4656594441, G4744413284, G4880911435, G4900465205, G4968846622, Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors, Energizing the failing heart, G5767140378, G5790172013, G5851709705, G5953624409, G6300988664, G6610179393, G6718544961, G7080048889, G7309355080, G7319818416, G7662726268, G8074704899, G82931992, G8316913482, G8471630636, Université de Paris, The RUSH (retention using selective hooks) system: a chemical-genetic system for the in vivo manipulation of intercellular communication, G8991455713
OpenAlex ID: W7213534369
FWCI:
Cites: 48
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Related to: 10