title: Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment.
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.
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York; Weill Cornell Medical College, 10065 New York, New York. Electronic address: dangelos@mskcc.org.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: D'Angelo
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shoushtari
authors.affiliation: Dept. of Pathology, Memorial Sloan Kettering Cancer Center, 10065 New York, New York.
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.affiliation: Dept. of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, 10065 New York, New York.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuk
authors.affiliation: Dept. of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, 10065 New York, New York.
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Qin
authors.affiliation: Weill Cornell Medical College, 10065 New York, New York; Melanoma and Immunotherapeutics Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York; Weill Cornell Medical College, 10065 New York, New York.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dickson
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York; Weill Cornell Medical College, 10065 New York, New York.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Gounder
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York; Weill Cornell Medical College, 10065 New York, New York.
authors.forename: Mary Louise
authors.initials: ML
authors.lastname: Keohan
authors.affiliation: Department of Medicine, Columbia University Medical Center, 10032 New York, New York.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.affiliation: Sarcoma Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center, 10065 New York, New York; Weill Cornell Medical College, 10065 New York, New York.
authors.forename: William D
authors.initials: WD
authors.lastname: Tap
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000737:chemistry* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000276:immunology*; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Immunotherapy; PD-1; PD-L1; Sarcoma; Tumor infiltrating lymphocyte CD3+, CD4+, CD8+, FOXP3+