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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.

cancer science

Impact of tumor microenvironment on the efficacy of epidermal growth factor receptor‐tyrosine kinase inhibitors in patients with   EGFR  ‐mutant non‐small cell lung cancer