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 journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalLung Cancer
Volume105
DOIs
Publication statusPublished - 2017 Mar 1

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Cytotoxic T-Lymphocytes
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Proteins
Cell Count
Neoplasms
Protein-Tyrosine Kinases
Disease-Free Survival
Multivariate Analysis
Immunohistochemistry
Mutation
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Soo, R. A., Kim, H. R., Asuncion, B. R., Fazreen, Z., Omar, M. F. M., Herrera, M. C., ... Cho, B. C. (2017). Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer. Lung Cancer, 105, 17-22. https://doi.org/10.1016/j.lungcan.2017.01.008
Soo, Ross A. ; Kim, Hye Ryun ; Asuncion, Bernadette Reyna ; Fazreen, Zul ; Omar, Mohamed Feroz Mohd ; Herrera, Maria Cynthia ; Yun Lim, Joey Sze ; Sia, Grace ; Soong, Richie ; Cho, Byoung Chul. / Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer. In: Lung Cancer. 2017 ; Vol. 105. pp. 17-22.
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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.",
author = "Soo, {Ross A.} and Kim, {Hye Ryun} and Asuncion, {Bernadette Reyna} and Zul Fazreen and Omar, {Mohamed Feroz Mohd} and Herrera, {Maria Cynthia} and {Yun Lim}, {Joey Sze} and Grace Sia and Richie Soong and Cho, {Byoung Chul}",
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Soo, RA, Kim, HR, Asuncion, BR, Fazreen, Z, Omar, MFM, Herrera, MC, Yun Lim, JS, Sia, G, Soong, R & Cho, BC 2017, 'Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer', Lung Cancer, vol. 105, pp. 17-22. https://doi.org/10.1016/j.lungcan.2017.01.008

Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer. / Soo, Ross A.; Kim, Hye Ryun; Asuncion, Bernadette Reyna; Fazreen, Zul; Omar, Mohamed Feroz Mohd; Herrera, Maria Cynthia; Yun Lim, Joey Sze; Sia, Grace; Soong, Richie; Cho, Byoung Chul.

In: Lung Cancer, Vol. 105, 01.03.2017, p. 17-22.

Research output: Contribution to journalArticle

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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

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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.

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Soo RA, Kim HR, Asuncion BR, Fazreen Z, Omar MFM, Herrera MC et al. Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer. Lung Cancer. 2017 Mar 1;105:17-22. https://doi.org/10.1016/j.lungcan.2017.01.008