TY - JOUR
T1 - Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer
AU - Soo, Ross A.
AU - Kim, Hye Ryun
AU - Asuncion, Bernadette Reyna
AU - Fazreen, Zul
AU - Omar, Mohamed Feroz Mohd
AU - Herrera, Maria Cynthia
AU - Yun Lim, Joey Sze
AU - Sia, Grace
AU - Soong, Richie
AU - Cho, Byoung Chul
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Cytotoxic T-lymphocyte antigen-4
KW - Epidermal growth factor receptor mutations
KW - Non-small cell lung cancer
KW - Programmed death ligand-1
KW - T-cell immunoglobulin and mucin-domain containing-3
UR - http://www.scopus.com/inward/record.url?scp=85009921566&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2017.01.008
DO - 10.1016/j.lungcan.2017.01.008
M3 - Article
C2 - 28236980
AN - SCOPUS:85009921566
VL - 105
SP - 17
EP - 22
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -