Ross A Soo1, Hye Ryun Kim2, Bernadette Reyna Asuncion3, Zul Fazreen3, Mohamed Feroz Mohd Omar3, Maria Cynthia Herrera3, Joey Sze Yun Lim3, Grace Sia3, Richie Soong3, Byoung-Chul Cho2. 1. Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore; School of Surgery, University of Western Australia, Perth, Australia; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. Electronic address: ross_soo@nuhs.edu.sg. 2. Division of Medical Oncology, Yonsei Cancer Center, Seoul, South Korea. 3. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
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.
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-L1tumor 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:TumorPD-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.
Authors: Ross A Soo; Joey Sze Yun Lim; Bernadette Reyna Asuncion; Zul Fazreen; Maria Cynthia Herrera; Mohd Feroz Mohd Omar; Nguyen Hoang Diem Phuong; Ju Ee Seet; Benhur Amanuel; Barry Iacopetta; David Byrne; Shona Hendry; Stephen Fox; Richie Soong Journal: Oncotarget Date: 2018-01-02