title: Infiltration of CD8 T Cells and Expression of PD-1 and PD-L1 in Synovial Sarcoma.
abstract: Tumors expressing programmed death ligand 1 (PD-L1) interact with the corresponding negative-signal generating immune receptor on the surface of CD8 T cells, PD-1, thereby suppressing antitumor activity. Therapeutics blocking this interaction have shown promise in various cancers by restoring functional antitumor T-cell activity. We explored the degree of PD-L1, PD-1, and CD8 expression in a retrospective analysis of 29 clinical synovial sarcoma samples. Quantitative immunohistochemistry and multiplex immunofluorescence were used to determine relative quantification of CD8+and PD-1+T cells and PD-L1 expression within the intratumor area and the interface between the tumor and the surrounding nontumor tissue (i.e., invasive margin), and colocalization of these factors, respectively. PD-L1, PD-1, and CD8 cell densities in the tumor-invasive margins were significantly higher in the metastatic tumors than the primary tumors (P < 0.01), and PD-L1, PD-1, and CD8 cell densities were all significantly positively correlated with one other (P < 0.0001). PD-1 cell density in the tumor-invasive margin was significantly associated with worse progression-free survival. Multiplex immunofluorescence demonstrated coexpression of PD-1 and CD8 on lymphocytes within the invasive margin, as well as relative proximity between PD-1+CD8 cells and PD-L1+tumor cells. Our results provide a preclinical rationale for screening of patients with synovial sarcoma for the colocalization of CD8, PD-1, and PD-L1, which may be a marker for response to PD-1 blockade therapy. Cancer Immunol Res; 5(2); 118-26. ©2016 AACR.
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Nowicki
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
authors.forename: Ryan
authors.initials: R
authors.lastname: Akiyama
authors.affiliation: Department of Pathology, University of California Los Angeles, Los Angeles, California.
authors.forename: Rong Rong
authors.initials: RR
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of California Los Angeles, Los Angeles, California.
authors.forename: I Peter
authors.initials: IP
authors.lastname: Shintaku
authors.affiliation: Department of General Internal Medicine, University of California Los Angeles, Los Angeles, California.|Department of Health Services Research, University of California Los Angeles, Los Angeles, California.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, California.|Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.|Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Tumeh
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Arun
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.|Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Christopher
authors.initials: C
authors.lastname: Denny
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.|Jonsson Comprehensive Cancer Center, Los Angeles, California.|Department of Orthopedics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. aribas@mednet.ucla.edu.|Jonsson Comprehensive Cancer Center, Los Angeles, California.|Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.|Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013584:Sarcoma, Synovial / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000401:mortality
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor