Neutralization of the autophagy-repressive tissue hormone DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) enhances anticancer immunosurveillance
Year: 2024
Type: editorial
Abstract: The plasma concentration of the macroautophagy/autophagy inhibitor DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) increases with aging and body mass index (BMI). Both advanced age and obesity are among the most important risk factors for the development of cancer. We observed that patients with cancer predisposition syndromes due to mutations in BRCA1, BRCA2 and TP53 exhibit abnormally high plasma DBI/ACBP levels. Additionally, patients without known cancer predisposition syndromes also manifest higher DBI/ACBP levels before imminent cancer diagnosis (within 0–3 years) as compared to age and BMI-matched controls who remain cancer-free. Thus, supranormal plasma DBI/ACBP constitutes a risk factor for later cancer development. Mouse experimentation revealed that genetic or antibody-mediated DBI/ACBP inhibition can delay the development or progression of cancers. In the context of chemoimmunotherapy, DBI/ACBP neutralization enhances tumor infiltration by non-exhausted effector T cells but reduces infiltration by regulatory T cells. This resulted in better cancer control in models of breast cancer, non-small cell lung cancer and sarcoma. We conclude that DBI/ACBP constitutes an actionable autophagy checkpoint for improving cancer immunosurveillance. Abbreviation: BMI, body mass index; CTL, cytotoxic T lymphocyte; DBI, diazepam binding inhibitor, acyl-CoA binding protein; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer; PDCD1/PD-1, programmed cell death 1; scRNA-seq, single-cell RNA sequencing; Treg, regulatory T cell.
Source: Autophagy
Authors: Léa Montégut, Isabelle Martins, Guido Kroemer
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Association pour la Recherche sur le Cancer, Seerave Foundation, Equipex, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Ligue Contre le Cancer, Institut Universitaire de France, Institut National Du Cancer, Direction Générale de l’offre de Soins, Ministère des Solidarités et de la Santé, Université de Paris, Labex Immuno-Oncology
Awards: G1056382719, G1152389130, G1168482666, G1190173965, G1348591106, Development of “smart” amplifiers of reactive oxygen species specific to aberrant polymorphonuclear neutrophils for treatment of inflammatory and autoimmune diseases, cancer and myeloablation., G1397743473, G1540355574, Next-generation phenotypic screening for oncological applications, G1647832332, G1716190585, G1743485262, G1846858737, G1912211089, G1963894250, G2109069054, G2161503289, G2203660494, Lung cancer prevention and interception, Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception., G2351262490, G2370373925, G2469459663, G2485135851, G2569310495, G2575938703, Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response., G2669570515, G2699422577, G2714391379, G2776565293, G282393413, G2992841218, G3116448791, G3225836234, G3231222199, Mitochondrial copper targeting to modulate inflammatory macrophages, G330243840, G3489513111, G3599999703, G3615399218, G3772543176, G3927921336, G4007257112, G4039294350, G4364925233, G4394515762, G4610811482, G461710914, G4656594441, G4707887143, G4746608011, G4752693786, G4787448540, G4880911435, G4900465205, G4968846622, G4990482369, G4992504448, G5111657532, G5121171980, G540687550, Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors, G5456938690, G5468290041, G5474765000, G5566697476, Energizing the failing heart, G5767140378, G5770080219, G5790172013, G5851709705, G5855436522, G5868422650, G5953624409, Metabolic and Autophagic Control by Acyl CoA Binding Protein (ACBP/DBI), G6292965458, G6300110603, G6300988664, G6318539078, G6458501901, G6467557300, G6491178327, G6558284573, G6610179393, G6654799599, G668953012, G6718544961, G6850463825, G69196502, G7017386022, G7041469554, G7075379671, G7080048889, G7101784390, G7309355080, G7319818416, G7339467324, G7371525705, G7374202952, G7562053067, G7662726268, G7839273552, G816800923, G82931992, G8316913482, G8471630636, Université de Paris, G8560148563, G8809306651, The RUSH (retention using selective hooks) system: a chemical-genetic system for the in vivo manipulation of intercellular communication, G8855315112, G8991455713, G915670629, G968191185
OpenAlex ID: W4403505834