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

• Published in: Human pathology Vol. 46; no. 3; pp. 357 - 365
• Main Authors: D’Angelo, Sandra P., MD, Shoushtari, Alexander N., MD, Agaram, Narasimhan P., MD, Kuk, Deborah, Qin, Li-Xuan, PhD, Carvajal, Richard D., MD, Dickson, Mark A., MD, Gounder, Mrinal, MD, Keohan, Mary Louise, MD, Schwartz, Gary K., MD, Tap, William D., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2015; Elsevier Limited
• Subjects: Adult; Aged; B7-H1 Antigen - analysis; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - pathology; Cytotoxicity; Female; Forkhead Transcription Factors - analysis; Humans; Immunohistochemistry; Immunotherapy; Laboratories; Life sciences; Ligands; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medical prognosis; Middle Aged; Multivariate analysis; Pathology; PD-1; PD-L1; Review boards; Sarcoma; Sarcoma - chemistry; Sarcoma - pathology; Tumor infiltrating lymphocyte CD3+, CD4+, CD8+, FOXP3; Tumor Microenvironment - immunology; Young Adult; PD-L1; Tumor infiltrating lymphocyte CD3+, CD4+, CD8+, FOXP3; Sarcoma; PD-1; Immunotherapy
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2014.11.001

Summary 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.