Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment

Hum Pathol. 2015 Mar;46(3):357-65. doi: 10.1016/j.humpath.2014.11.001. Epub 2014 Nov 15.

Abstract

The prognostic and predictive implications of programmed death-ligand 1 (PD-L1) is unknown in sarcoma. We sought to examine the immune milieu in sarcoma specimens. We evaluated PD-L1 expression by immunohistochemistry in sarcoma specimens and quantified tumor-infiltrating lymphocytes (TIL). We correlated expression with clinical parameters and outcomes. Fifty sarcoma patients treated at Memorial Sloan Kettering Cancer Center were selected. Using the DAKO PD-L1 immunohistochemistry assay and archival formalin-fixed paraffin-embedded tissue specimens; PD-L1 expression was examined. Macrophage and lymphocyte PD-L1 status was determined qualitatively. TIL was quantified. Associations between PD-L1 expression in tumor, macrophages and lymphocytes, TIL and clinical-pathological characteristics were performed. The median age was 46 years (range, 22-76), and 66% of patients were men. Tumor, lymphocyte and macrophage PD-L1 expression was noted in 12%, 30% and 58%, respectively, with the highest prevalence in gastrointestinal stromal tumors (29%). Lymphocyte and macrophage infiltration was present in 98% and 90%, respectively. There was no association between clinical features, overall survival and PD-L1 expression in tumor or immune infiltrates. Lymphocyte and macrophage infiltration is common in sarcoma, but PD-L1 tumor expression is uncommon in sarcoma with the highest frequency observed in gastrointestinal stromal tumors. There was no association between PD-L1 expression, TIL and clinicopathological features and overall survival; however, this is limited by the heterogenous patient sample and minimal death events in the studied cohort.

Keywords: Immunotherapy; PD-1; PD-L1; Sarcoma; Tumor infiltrating lymphocyte CD3+, CD4+, CD8+, FOXP3+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis*
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Forkhead Transcription Factors / analysis
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Sarcoma / chemistry*
  • Sarcoma / pathology*
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors