Open AccessImpact of tumor microenvironment on the efficacy of epidermal growth factor receptor‐tyrosine kinase inhibitors in patients with EGFR ‐mutant non‐small cell lung cancer
Author(s) -
Matsumoto Yoshiya,
Sawa Kenji,
Fukui Mitsuru,
Oyanagi Jun,
Izumi Motohiro,
Ogawa Koichi,
Suzumura Tomohiro,
Watanabe Tetsuya,
Kaneda Hiroyasu,
Mitsuoka Shigeki,
Asai Kazuhisa,
Kimura Tatsuo,
Yamamoto Nobuyuki,
Koh Yasuhiro,
Kawaguchi Tomoya
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14156
Subject(s) - medicine , cd8 , epidermal growth factor receptor , immunohistochemistry , lung cancer , tumor microenvironment , cancer , tyrosine kinase , lung , receptor , gastroenterology , pathology , cancer research , immune system , immunology
We retrospectively investigated the impact of the tumor microenvironment ( TME ) on the efficacy of epidermal growth factor receptor ( EGFR )‐tyrosine kinase inhibitors ( TKI s) as first‐line treatment in 70 patients with advanced EGFR ‐mutant non‐small cell lung cancer and who were seen at Osaka City University Hospital (Osaka, Japan) between August 2013 and December 2017. Using immunohistochemical staining with 28‐8 and D7U8C Abs, the tumor proportion score was assessed for programmed cell death‐1 ligand‐1 ( PD ‐L1), as high (50% or more) or low (less than 50%), and ligand‐2 ( PD ‐L2) expression, respectively. The extent of CD 8 + tumor‐infiltrating lymphocytes was evaluated on a scale of 0‐3, with 0‐1 as low and 2‐3 as high. The TME of the 52 evaluable pretreatment specimens was categorized into 4 subtypes, according to the respective PD ‐L1 tumor proportion and CD 8 + scores, as follows: (a) high/high (13.5%, n = 7); (b) low/low (42.3%, n = 22); (c) high/low (17.3%, n = 9); and (d) low/high (26.9%, n = 14). Expression of PD ‐L2 was significantly the highest in type 1 (57.1% vs 4.5% vs 11.1% vs 7.1%, respectively; P = .0090). Response rate was significantly the lowest in type 1 (14.3% vs 81.8% vs 66.7% vs 78.6%, respectively; P = .0085). Progression‐free survival was the shortest in type 1 and the longest in type 4 (median, 2.4 vs 11.3 vs 8.4 vs 17.5 months, respectively; P = .77). The efficacy of EGFR ‐ TKI s differed according to the TME , and the phenotype with high PD ‐L1 and CD 8 + expression might be the subset that would poorly benefit from such treatment.