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Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer

Authors
 Ross A. Soo  ;  Hye Ryun Kim  ;  Bernadette Reyna Asuncion  ;  Zul Fazreen  ;  Mohamed Feroz Mohd Omar  ;  Maria Cynthia Herrera  ;  Joey Sze Yun Lim  ;  Grace Sia  ;  Richie Soong  ;  Byoung-Chul Cho 
Citation
 LUNG CANCER, Vol.105 : 17-22, 2017 
Journal Title
LUNG CANCER
ISSN
 0169-5002 
Issue Date
2017
MeSH
Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/metabolism ; Biomarkers, Tumor/metabolism ; CD3 Complex/metabolism ; CTLA-4 Antigen/metabolism ; Carcinoma, Non-Small-Cell Lung/genetics ; Female ; Hepatitis A Virus Cellular Receptor 2/metabolism ; Humans ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Mutation ; Programmed Cell Death 1 Receptor/metabolism ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Receptor, Epidermal Growth Factor/genetics ; Survival Analysis ; Treatment Outcome
Keywords
Cytotoxic T-lymphocyte antigen-4 ; Epidermal growth factor receptor mutations ; Non-small cell lung cancer ; Programmed death ligand-1 ; T-cell immunoglobulin ; mucin-domain containing-3
Abstract
OBJECTIVES:

To characterize the expression of PD-L1, PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS:

Samples from 90 patients with newly diagnosed advanced stage NSCLC harboring EGFR mutations and treated with first line EGFR tyrosine kinase inhibitors (TKI) within 3 months of diagnosis were stained for CTLA-4, PD-L1, PD-1, TIM-3 and CD3 expression by immunohistochemistry.

RESULTS:

PD-L1 was present in at least 1% of immune and tumor cells in 44% and 59% of samples, respectively. In multivariate analysis, increased CD3 immune shaped cell (ISC) counts (HR 2.805, p=0.034) and high PD-L1 tumor H-score (HR 3.805, p=0.022) was associated with a shorter progression free survival and high CTLA-4 ISC counts was associated with borderline overall survival significance (HR 1.054, p=0.061).

CONCLUSION:

Tumor PD-L1 expression was significantly associated with a shorter PFS whereas immune cell CTLA-4 may be prognostic for OS. Our findings support the ongoing development of CTLA-4 and PD1/PD-L1 inhibitors in this important molecularly defined subset of lung adenocarcinoma.
Full Text
https://www.sciencedirect.com/science/article/pii/S0169500217300090
DOI
10.1016/j.lungcan.2017.01.008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160523
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