title: Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas.
abstract: Recently, the possibility of PD1 pathway-targeted therapy has been extensively studied in various human malignant tumors. However, no previous study has investigated their potential application for soft-tissue sarcomas (STS). In this study, we evaluated the clinical impact of intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression in tumor cells in 105 cases of STS. Intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression were seen in 65% and 58% of STS, respectively. Both PD1-positivity and PD-L1 expression were significantly associated with advanced clinicopathological parameters such as higher clinical stage, presence of distant metastasis, higher histological grade, poor differentiation of tumor, and tumor necrosis. Moreover, both PD1-positivity and PD-L1 positivity were independent prognostic indicators of overall survival (OS) and event-free survival (EFS) of STS by multivariate analysis. In addition, the combined pattern of PD1- and PD-L1-positivity was also an independent prognostic indicator for OS and EFS by multivariate analysis. The patents with a PD1(+)/PD-L1(+) pattern had the shortest survival time. In conclusion, this study is the first to demonstrate that the infiltration of PD1 positive lymphocytes and PD-L1 expression in STS cells could be used as novel prognostic indicators for STS. Moreover, the evaluation of PD1- and PD-L1-positivity in STS is also available as possible criteria for selection of patients suitable for PD1-based immunotherapy.
authors.affiliation: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Jung Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Moon
authors.affiliation: Department of Preventive Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Sajeev
authors.initials: S
authors.lastname: Wagle
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Myoung Ja
authors.initials: MJ
authors.lastname: Chung
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Myoung Jae
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009363:Neoplasm Proteins / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D012189:Retrospective Studies; D012509:Sarcoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor