title: PD-1, PD-L1, PD-L2 expression in the chordoma microenvironment.
abstract: Chordomas are rare malignant tumors that are postulated to arise from remnants of the notochord. Currently, the interaction between chordomas and the host immune system is poorly understood. The checkpoint protein, PD-1 is expressed by circulating lymphocytes and is a marker of activation and exhaustion. Its ligands, PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273), are expressed on a variety of human cancers; however this pathway has not been previously reported in chordomas. We used flow cytometric and RT-PCR analysis in three established primary and recurrent chordoma cell lines (U-CH1, U-CH2, and JHC7) as well as immunohistochemical analysis of chordoma tissues from 10 patients to identify and localize expression of PD-1 pathway proteins. PD-1 ligands are not constitutively expressed by chordoma cells, but their expression is induced in the setting of pro-inflammatory cytokines in all cell lines examined. In paraffin embedded tissues, we found that tumor infiltrating lymphocytes expressed PD-1 in 3/6 cases. We also found that, although chordoma cells did not express significant levels of PD-L1, PD-L1 expression was observed on tumor-infiltrating macrophages and tumor infiltrating lymphocytes. Our study suggests that PD-1, PD-L1, and PD-L2 are present in the microenvironment of a subset of chordomas analyzed. Future studies are needed to evaluate the contribution of the PD-1 pathway to the immunosuppressive microenvironment of chordomas.
authors.affiliation: Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mathios
authors.forename: Jacob
authors.initials: J
authors.lastname: Ruzevick
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jackson
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Sagar R
authors.initials: SR
authors.lastname: Shah
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burger
authors.forename: Edward F
authors.initials: EF
authors.lastname: McCarthy
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D002817:Chordoma / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D010784:Photomicrography; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger