Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy

Eun Ah Choe, Yoon Jin Cha, Jae Hwan Kim, Kyoung Ho Pyo, Min Hee Hong, Seong Yong Park, Hyo Sup Shim, Inkyung Jung, Chang Young Lee, ByoungChul Cho, Hye Ryun Kim

Research output: Contribution to journalArticle

Abstract

Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. Materials and methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. Results: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). Conclusions: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalLung Cancer
Volume136
DOIs
Publication statusPublished - 2019 Oct 1

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Tumor-Infiltrating Lymphocytes
Non-Small Cell Lung Carcinoma
Lymphocyte Count
Ligands
T-Lymphocytes
Survival
Therapeutics
Recurrence
Neoplasms
Survival Analysis
Korea
Immunotherapy
Up-Regulation
Down-Regulation
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Choe, Eun Ah ; Cha, Yoon Jin ; Kim, Jae Hwan ; Pyo, Kyoung Ho ; Hong, Min Hee ; Park, Seong Yong ; Shim, Hyo Sup ; Jung, Inkyung ; Lee, Chang Young ; Cho, ByoungChul ; Kim, Hye Ryun. / Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy. In: Lung Cancer. 2019 ; Vol. 136. pp. 30-36.
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title = "Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy",
abstract = "Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. Materials and methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. Results: More than half patients (52{\%}) showed up- or downregulation of PD-L1 expression, and most patients (81{\%}) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). Conclusions: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.",
author = "Choe, {Eun Ah} and Cha, {Yoon Jin} and Kim, {Jae Hwan} and Pyo, {Kyoung Ho} and Hong, {Min Hee} and Park, {Seong Yong} and Shim, {Hyo Sup} and Inkyung Jung and Lee, {Chang Young} and ByoungChul Cho and Kim, {Hye Ryun}",
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Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy. / Choe, Eun Ah; Cha, Yoon Jin; Kim, Jae Hwan; Pyo, Kyoung Ho; Hong, Min Hee; Park, Seong Yong; Shim, Hyo Sup; Jung, Inkyung; Lee, Chang Young; Cho, ByoungChul; Kim, Hye Ryun.

In: Lung Cancer, Vol. 136, 01.10.2019, p. 30-36.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy

AU - Choe, Eun Ah

AU - Cha, Yoon Jin

AU - Kim, Jae Hwan

AU - Pyo, Kyoung Ho

AU - Hong, Min Hee

AU - Park, Seong Yong

AU - Shim, Hyo Sup

AU - Jung, Inkyung

AU - Lee, Chang Young

AU - Cho, ByoungChul

AU - Kim, Hye Ryun

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. Materials and methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. Results: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). Conclusions: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.

AB - Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8+ TIL counts following CCRT and their relationship to treatment outcome. Materials and methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8+ TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. Results: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8+ TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8+ TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). Conclusions: CCRT dynamically alters PD-L1 expression and CD8+ TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.

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