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Journal article
Blockade of Tumor-Expressed PD-1 promotes lung cancer growth
Oncoimmunology, v 7(4), pp e1408747-e1408747
03 Apr 2018
PMID: 29632720
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and lung cancer-specific markers in resected lung cancer tissues. We further investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in-vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished viability. PD-1 blockade accelerated growth of M109-xenograft tumors with increased proliferation and decreased apoptosis in immune-deficient mice. This represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential mechanism by which PD-1 blockade may promote cancer growth.
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Details
- Title
- Blockade of Tumor-Expressed PD-1 promotes lung cancer growth
- Creators
- Shisuo Du - Thomas Jefferson UniversityNeal McCall - Thomas Jefferson UniversityKyewon Park - Thomas Jefferson UniversityQing Guan - Fudan University Shanghai Cancer CenterPaolo Fontina - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityTingting Zhan - Thomas Jefferson UniversityAdam P. Dicker - Thomas Jefferson UniversityBo Lu - Thomas Jefferson University
- Publication Details
- Oncoimmunology, v 7(4), pp e1408747-e1408747
- Publisher
- Taylor & Francis
- Grant note
- 1R21CA178229-01 and DOD LC150118 / NCI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000428277500015
- Scopus ID
- 2-s2.0-85041173433
- Other Identifier
- 991019176802204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Oncology