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

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

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalLung Cancer
Publication statusPublished - 2017 Mar 1

Bibliographical note

Funding Information:
This study was supported by the National Medical Research CouncilNMRC/CG/012/2013, the National Research Foundation Singapore, the Singapore Ministry of Education under its Research Centres of Excellence initiative, and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C1440).

Publisher Copyright:
© 2017 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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