Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Broad Institute · Brigham and Women's Hospital · +7 more institutions
Abstract
UNLABELLED: 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 EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs 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…
Citation impact
- FWCI
- 37.68
- Percentile
- 100%
- References
- 37
Authors
27- EAEsra A. Akbay
Broad Institute, Brigham and Women's Hospital, Harvard University, Universitat de València, Massachusetts General Hospital, Dana-Farber Cancer Institute, Ludwig Cancer Research
- SKShohei Koyama
Broad Institute, University of North Carolina at Chapel Hill, Brigham and Women's Hospital, Harvard University, Universitat de València, Massachusetts General Hospital, Dana-Farber Cancer Institute, Ludwig Cancer Research
- JCJulián Carretero
Broad Institute, University of North Carolina at Chapel Hill, Brigham and Women's Hospital, Harvard University, Universitat de València, Loyola University Chicago, Massachusetts General Hospital, Dana-Farber Cancer Institute, Ludwig Cancer Research
- AAAbigail Altabef
Broad Institute, University of North Carolina at Chapel Hill, Brigham and Women's Hospital, Harvard University, Universitat de València, Massachusetts General Hospital, Dana-Farber Cancer Institute, Ludwig Cancer Research
- JHJeremy H. Tchaicha
Broad Institute, Brigham and Women's Hospital, Harvard University, Universitat de València, Massachusetts General Hospital, Dana-Farber Cancer Institute, Ludwig Cancer Research
Topics & keywords
- Cancer research
- Immune system
- Proinflammatory cytokine
- Lung cancer
- PD-L1
- T cell
- CTL*
- Downregulation and upregulation
- Good health and well-being