Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

DSpace/Manakin Repository

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

Citable link to this page

 

 
Title: Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Author: Akbay, E; Koyama, S.; Carretero, J.; Altabef, A.; Tchaicha, J. H.; Christensen, Camilla Laulund; Mikse, O. R.; Cherniack, Andrew David; Beauchamp, Ellen Monica; Pugh, T; Wilkerson, M. D.; Fecci, P; Butaney, M.; Reibel, J. B.; Soucheray, M.; Cohoon, T. J.; Janne, Pasi Antero; Meyerson, Matthew Langer; Hayes, D. N.; Shapiro, Geoffrey Ira; Shimamura, T; Sholl, Lynette Marie; Rodig, Scott J.; Freeman, Gordon James; Hammerman, Peter Seth; Dranoff, G; Wong, Kwok-Kin

Note: Order does not necessarily reflect citation order of authors.

Citation: Akbay, E. A., S. Koyama, J. Carretero, A. Altabef, J. H. Tchaicha, C. L. Christensen, O. R. Mikse, et al. 2013. “Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors.” Cancer Discovery 3 (12) (September 27): 1355–1363. doi:10.1158/2159-8290.cd-13-0310.
Full Text & Related Files:
Abstract: The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition.
Published Version: doi:10.1158/2159-8290.CD-13-0310
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864135/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32706162
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters