Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade.
Détails
ID Serval
serval:BIB_45BBFC2841DC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade.
Périodique
Cancer cell
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Statut éditorial
Publié
Date de publication
08/02/2021
Peer-reviewed
Oui
Volume
39
Numéro
2
Pages
193-208.e10
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the Kras <sup>LSL-G12D/+</sup> ;p53 <sup>f/f</sup> autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.
Mots-clé
Animals, Antigens, Neoplasm/immunology, Cell Line, Cell Line, Tumor, HEK293 Cells, Humans, Immune Checkpoint Inhibitors/immunology, Immunotherapy, Adoptive/methods, Lung Neoplasms/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptor Tyrosine Kinase-like Orphan Receptors/immunology, Receptors, Antigen, T-Cell/immunology, Receptors, Chimeric Antigen/immunology, T-Lymphocytes/immunology, Tumor Microenvironment/immunology, CAR-T cells, CXCR3, CXCR6, KP, ROR1, alveolar macrophage, immunogenic cell death, lung adenocarcinoma, oxaliplatin
Pubmed
Web of science
Création de la notice
28/02/2022 12:45
Dernière modification de la notice
23/03/2024 8:24