Oncotarget

Research Papers:

Changes in PD-L1 expression according to tumor infiltrating lymphocytes of acquired EGFR-TKI resistant EGFR-mutant non-small-cell lung cancer

Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang and Sook-Hee Hong _

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Oncotarget. 2017; 8:107630-107639. https://doi.org/10.18632/oncotarget.22582

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Abstract

Tae-Jung Kim1, Soon Auck Hong2, Okran Kim3, Seung Joon Kim4, Ji-Hyun Yang5, Eun Kyo Joung5, Jin-Hyoung Kang5 and Sook-Hee Hong3,5

1Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

2Department of Pathology, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea

3Cancer Research Institute, The Catholic University of Korea, Seoul, Korea

4Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

5Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to:

Sook-Hee Hong, email: ssuki76@catholic.ac.kr

Keywords: epidermal growth factor receptor; programmed death receptor ligand 1; CD8+ tumor infiltrating lymphocyte; non-small cell lung cancer

Received: August 14, 2017     Accepted: October 31, 2017     Published: November 21, 2017

ABSTRACT

Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor.

Results: TPS≥1% for PD-L1 and low CD8+ TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40.5%), with 10 (21.2%) showing higher levels in the resistant biopsy (cohort B). Among the post-TKI high TPS groups, median PFS with low post- TKI CD8+ TIL scores treated with EGFR-TKIs (6.6 months) was significantly lower than that for the other patients (14.2 months; P = 0.015).

Conclusions: The change of PD-L1 expression was accompanied by dynamic change in CD8+ TILs and might reflect diverse mechanism of resistance to EGFR-TKI therapy.

Material and Methods: We identified 69 patients (cohort A) with sufficient post-TKI tumor tissues and 47 patients (cohort B) with paired tumor tissues available. TPS for PD-L1 expression of tumor cells and CD8+ TILs score in tumor specimens were determined by immunohistochemistry.


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