Clinicopathologic Features and Immune Microenvironment of Non-Small-cell Lung Cancer With Primary Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Takashima, Yuta; Sakakibara-Konishi, Jun; Hatanaka, Yutaka; Hatanaka, Kanako C.; Ohhara, Yoshihito; Oizumi, Satoshi; Hida, Yasuhiro; Kaga, Kichizo; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Matsuno, Yoshihiro; Nishimura, Masaharu

Clinicopathologic Features and Immune Microenvironment of Non-Small-cell Lung Cancer With Primary Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Takashima, Yuta; Sakakibara-Konishi, Jun; Hatanaka, Yutaka et al.

Clinical lung cancer, 2018, 19(4), 352-359

Permalink : https://hdl.handle.net/2115/74825

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アクセス権	open access
URI	https://hdl.handle.net/2115/74825
タイトル	Clinicopathologic Features and Immune Microenvironment of Non-Small-cell Lung Cancer With Primary Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
著者	Takashima, Yuta ; Sakakibara-Konishi, Jun ; Hatanaka, Yutaka ; Hatanaka, Kanako C. ; Ohhara, Yoshihito ; Oizumi, Satoshi ; Hida, Yasuhiro ; Kaga, Kichizo ; Kinoshita, Ichiro ; Dosaka-Akita, Hirotoshi ; Matsuno, Yoshihiro ; Nishimura, Masaharu
著者名 Takashima, Yuta
e-Rad_Researcher 50374278 著者名 Sakakibara-Konishi, Jun
e-Rad_Researcher 30589924 著者名 Hatanaka, Yutaka
著者名 Hatanaka, Kanako C.
著者名 Ohhara, Yoshihito
e-Rad_Researcher 10421968 著者名 Oizumi, Satoshi
e-Rad_Researcher 30399919 著者名 Hida, Yasuhiro
e-Rad_Researcher 80224335 著者名 Kaga, Kichizo
e-Rad_Researcher 40343008 著者名 Kinoshita, Ichiro
e-Rad_Researcher 70222528 著者名 Dosaka-Akita, Hirotoshi
e-Rad_Researcher 00199829 著者名 Matsuno, Yoshihiro
e-Rad_Researcher 00208224 著者名 Nishimura, Masaharu
言語	英語
キーワード	EGFR-TKI
	NSCLC
	PD-L1
	Smoking
	Tumor-infiltrating lymphocytes
	primary resistance
発行日	2018-07
出版者	Elsevier
収録物名	Clinical lung cancer
巻(号)	19(4)
ページ	352-359
抄録	We evaluated the clinical and immunopathological features of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors. The rate of smoking was significantly higher in primary resistance. The immune microenvironment characterized by low total tumor infiltrating lymphocytes and negative programmed death ligand 1 correlated significantly with primary resistance. Background: Approximately 20% to 30% of nonesmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumorinfiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC. However, few studies have directly focused on the relationship between the tumor immunemicroenvironment and primary resistance to EGFR-TKIs. Materials and Methods: The characteristics of 124 NSCLC patients with EGFR mutations who had received EGFR-TKIs were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFRTKI treatment were assessed for the density of TILs expressing CD4 or CD8 and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% of the patients (17 of 124). A significant difference in smoking history was observed between patients with primary resistance and those with noneprimary resistance. A lower density of total TILs and negative PD-L1 expression on immunohistochemical analysis correlated significantly with primary resistance, in contrast to that with noneprimary resistance. Moreover, the negative PD-L1 expression with low TIL density, indicating immune ignorant phenotype of tumor microenvironment, was observed in those with primary resistance with a significant difference. Conclusion: Smoking and immune ignorance in the tumor microenvironment might result in primary resistance to EGFR-TKIs.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1525-7304
関連情報	PMID 29544718
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cllc.2018.02.004