title: Programmed Cell Death Ligand 1 Expression in Resected Lung Adenocarcinomas: Association with Immune Microenvironment.
abstract: Programmed cell death ligand 1 (PD-L1) expression on tumor cells can be upregulated via activation of CD8+cytotoxic T lymphocytes (CTLs) or the T helper cell (Th1) pathway, counterbalancing the CTL/Th1 microenvironment. However, PD-L1 expression in association with subtypes of tumor-associated lymphocytes and molecular alterations has not been well characterized in lung adenocarcinomas.
  
  
  
  PD-L1 expression was evaluated in 261 resected lung adenocarcinomas using tissue microarrays and various scoring systems, and was correlated with clinicopathologic/molecular features, including the extent/subtype of tumor-associated lymphocytes (i.e., CD8, T-bet [Th1 transcription factor], and GATA3 [Th2 transcription factor]), and patient outcomes.
  
  
  
  PD-L1 expression was present in 129 (49%), 95 (36.5%), and 62 (24%) cases using cutoffs of ≥1%, ≥5%, and ≥50%, respectively, 98 (38%) by H score and 72 (28%) by immune score. PD-L1 expression was associated with abundant CD8+and/or T-bet+tumor-infiltrating lymphocytes and EGFR wild-type, significant smoking history, and aggressive pathologic features. In addition, concurrent PD-L1 expression and abundant CD8+tumor-associated lymphocytes were seen in 25% of KRAS mutants or cases with no alterations by clinical molecular testing as opposed to only 7.4% of EGFR mutants. PD-L1 expression was significantly associated with decreased progression-free and overall survival rates by univariate analysis, but not by multivariate analysis.
  
  
  
  PD-L1 expression in resected lung adenocarcinomas is frequently observed in the presence of CTL/Th1 microenvironment, in particular in those with KRAS mutations or no common molecular alterations, suggesting that blockade of the PD-1/PD-L1 axis may be a promising treatment strategy to reinstitute active immune response for at least a subset of such patient populations.
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors: Tiffany G
authors: TG
authors: Huynh
authors: Department of Epidemiology and Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors: Vicente
authors: V
authors: Morales-Oyarvide
authors: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
authors: Meghan J
authors: MJ
authors: Campo
authors: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors: Justin F
authors: JF
authors: Gainor
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors: Emine
authors: E
authors: Bozkurtlar
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors: Hironori
authors: H
authors: Uruga
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors: Ling
authors: L
authors: Zhao
authors: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
authors: Maria
authors: M
authors: Gomez-Caraballo
authors: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors: Aaron N
authors: AN
authors: Hata
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors: Eugene J
authors: EJ
authors: Mark
authors: Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors: Michael
authors: M
authors: Lanuti
authors: Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors: Jeffrey A
authors: JA
authors: Engelman
authors: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts. Electronic address: mminokenudson@partners.org.
authors: Mari
authors: M
authors: Mino-Kenudson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: KRAS mutation; Lung adenocarcinoma; PD-L1; Smoking; Tumor microenvironment