Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance - Immunologie des tumeurs et immunothérapie contre le cancer - UMR 1015
Article Dans Une Revue Molecular Cancer Année : 2024

Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance

1 IGR - Institut Gustave Roussy
2 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
3 Tongji Medical College [HUST]
4 HUST - Huazhong University of Science and Technology [Wuhan]
5 Université Paris-Saclay
6 ITIC - Immunologie anti-tumorale et immunothérapie des cancers
7 Università del Piemonte Orientale - Dipartimento DISIT Italy
8 INIBIC - Instituto de Investigación Biomédica de A Coruña [La Corogne, Espagne]
9 U932 - Immunité et cancer
10 CNIO - Centro Nacional de Investigaciones Oncologicas / Spanish National Cancer Research Centre [Madrid, Espagne]
11 Institut Curie - Genomics of Excellence (ICGex) Platform
12 PSL - Université Paris Sciences et Lettres
13 AP-HP - Hopital Saint-Louis [AP-HP]
14 CR CHUM - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
15 CHUM - Centre Hospitalier de l'Université de Montréal
16 METSY - Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques
17 Hôpital Nord [CHU - APHM]
18 CRCM - Centre de Recherche en Cancérologie de Marseille
19 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
20 Réseau National Alimentation Cancer Recherche (réseau NACRe)
21 CICBT - Centre d'Investigation Clinique Biothérapie
22 Département de médecine oncologique [Gustave Roussy]
23 CRC - UMR_S 1138 - Métabolisme, Cancer et Immunité
24 IUF - Institut universitaire de France
25 SIRIC CARPEM - Cancer Research and Personalized Medicine - CARPEM [Paris]
26 HEGP - Hôpital Européen Georges Pompidou [APHP]

Résumé

Background: The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or 'endozepine') increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods: We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results: Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion: These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.
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hal-04704596 , version 1 (21-09-2024)

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Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, et al.. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance. Molecular Cancer, 2024, 23 (1), pp.187. ⟨10.1186/s12943-024-02098-5⟩. ⟨hal-04704596⟩
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