Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas

PLoS One. 2013 Dec 11;8(12):e82870. doi: 10.1371/journal.pone.0082870. eCollection 2013.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / immunology*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immunotherapy
  • Lymphocytes* / immunology
  • Lymphocytes* / pathology
  • Male
  • Middle Aged
  • Necrosis
  • Neoplasm Proteins / immunology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Retrospective Studies
  • Sarcoma* / immunology
  • Sarcoma* / mortality
  • Sarcoma* / pathology
  • Sarcoma* / therapy
  • Survival Rate

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grant support

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0028928). National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2011-0028928). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.