title: Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: Impact on treatment efficacy and alteration in expression after chemotherapy.
abstract: To understand the clinical impact of PD-1/L1 expression in thymoma (TM) and thymic carcinoma (TC), we evaluated the frequency of PD-1/L1 expression in pre/post chemotherapy specimens and the correlation with the treatment efficacy.
  
  
  
  The expression of PD-1/L1 was evaluated using immunohistochemistry in patients with TM or TC treated with chemotherapy between 2000 and 2014. Using formalin-fixed, paraffin-embedded tissue samples and a PD-L1 antibody, the expression of PD-L1 in the TM and TC specimens was reported in terms of the H-score (0-300), with a score ≥1 being defined as positive. The PD-1 expression in the tumor-infiltrating immune cells was evaluated based on the intensity (0-3) of staining using a PD-1 antibody. The objective response rate, progression-free survival, and the difference in PD-1/L1 expression between the pre/post chemotherapy were evaluated.
  
  
  
  Thirty patients (TM/TC 12/18) were evaluated. PD-L1 positivity were TM/TC 67%/41%. Within the PD-L1 positive/negative populations, the objective response rates were 50%/0% for TM and 14%/20% for TC. No significant differences in progression-free survival were seen according to the PD-L1 expression status. Increases in both the PD-L1 and PD-1 scores were observed after chemotherapy in six serial pre/post chemotherapy TM specimens, with a mean PD-L1 score and a median PD-1 intensity of 42/93, and 0/2.5, respectively.
  
  
  
  The substantially high expression of PD-L1 and the increase in PD-L1 and PD-1 expression after chemotherapy supports anti-PD-1/L1 drugs therapy for TM and TC as well as the development of a strategy for its sequential use after chemotherapy.
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Katsuya
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: hhorinou@ncc.go.jp.
authors: Hidehito
authors: H
authors: Horinouchi
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Tetsuhiko
authors: T
authors: Asao
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Shinsuke
authors: S
authors: Kitahara
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Yasushi
authors: Y
authors: Goto
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Shintaro
authors: S
authors: Kanda
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Experimental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Fujiwara
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Nokihara
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Experimental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan.
authors: Noboru
authors: N
authors: Yamamoto
authors: Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
authors: Shun-Ichi
authors: S
authors: Watanabe
authors: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan; Department of Pathology and Laboratory Medicine Kansai Medical University, Japan.
authors: Koji
authors: K
authors: Tsuta
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Yuichiro
authors: Y
authors: Ohe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Chemotherapy; Immunogenicity; PD-1; PD-L1; Thymic carcinoma; Thymoma