Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_765E95D84B97
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors.
Périodique
Journal for immunotherapy of cancer
Auteur(s)
Ayeni D., Miller B., Kuhlmann A., Ho P.C., Robles-Oteiza C., Gaefele M., Levy S., de Miguel F.J., Perry C., Guan T., Krystal G., Lockwood W., Zelterman D., Homer R., Liu Z., Kaech S., Politi K.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Statut éditorial
Publié
Date de publication
10/07/2019
Peer-reviewed
Oui
Volume
7
Numéro
1
Pages
172
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: epublish
Résumé
Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) like erlotinib are effective for treating patients with EGFR mutant lung cancer; however, drug resistance inevitably emerges. Approaches to combine immunotherapies and targeted therapies to overcome or delay drug resistance have been hindered by limited knowledge of the effect of erlotinib on tumor-infiltrating immune cells.
Using mouse models, we studied the immunological profile of mutant EGFR-driven lung tumors before and after erlotinib treatment.
We found that erlotinib triggered the recruitment of inflammatory T cells into the lungs and increased maturation of alveolar macrophages. Interestingly, this phenotype could be recapitulated by tumor regression mediated by deprivation of the EGFR oncogene indicating that tumor regression alone was sufficient for these immunostimulatory effects. We also found that further efforts to boost the function and abundance of inflammatory cells, by combining erlotinib treatment with anti-PD-1 and/or a CD40 agonist, did not improve survival in an EGFR-driven mouse model.
Our findings lay the foundation for understanding the effects of TKIs on the tumor microenvironment and highlight the importance of investigating targeted and immuno-therapy combination strategies to treat EGFR mutant lung cancer.
Mots-clé
Animals, Antineoplastic Agents/therapeutic use, ErbB Receptors/genetics, ErbB Receptors/immunology, Erlotinib Hydrochloride/therapeutic use, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Lung Neoplasms/immunology, Mice, Transgenic, Mutation, Oncogenes, Protein Kinase Inhibitors/therapeutic use, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Tumor Microenvironment/drug effects, Tumor Microenvironment/immunology, EGFR, Immunotherapies, Lung cancer, Mouse models, Targeted therapies
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/07/2019 18:26
Dernière modification de la notice
15/01/2021 8:10
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