T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1759 views | HTML 3047 views | ?
Christian Spurny1, Sareetha Kailayangiri1, Bianca Altvater1, Silke Jamitzky1, Wolfgang Hartmann2, Eva Wardelmann2, Andreas Ranft1,3, Uta Dirksen1,3, Susanne Amler4, Jendrik Hardes5,4, Maike Fluegge1, Jutta Meltzer1, Nicole Farwick1, Lea Greune1 and Claudia Rossig1,6
1Department of Pediatric Hematology and Oncology, University Children´s Hospital Muenster, Muenster, Germany
2Gerhard Domagk Institute of Pathology, University of Muenster, Muenster, Germany
3University Hospital Essen, Pediatrics III, West German Cancer Centre, Essen, Germany
4Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany
5Department of Orthopedic Surgery, University Hospital Muenster, Muenster, Germany
6Cells-in-Motion Cluster of Excellence (EXC 1003 – CiM), University of Muenster, Germany
Claudia Rossig, email: [email protected]
Keywords: Ewing sarcoma; HLA-G; T cells; cellular immunotherapy; immune checkpoints
Received: September 08, 2017 Accepted: October 27, 2017 Published: December 22, 2017
Ewing sarcoma (EwS) is an aggressive mesenchymal cancer of bones or soft tissues. The mechanisms by which this cancer interacts with the host immune system to induce tolerance are not well understood. We hypothesized that the non-classical, immune-inhibitory HLA-molecule HLA-G contributes to immune escape of EwS. While HLA-Gpos suppressor T cells were not increased in the peripheral blood of EwS patients, HLA-G was locally expressed on the tumor cells and/or on infiltrating lymphocytes in 16 of 47 pretherapeutic tumor biopsies and in 4 of 12 relapse tumors. HLA-G expression was not associated with risk-related patient variables or response to standard chemotherapy, but with significantly increased numbers of tumor-infiltrating CD3+ T cells compared to HLA-Gneg EwS biopsies. In a mouse model, EwS xenografts after adoptive therapy with tumor antigen-specific CAR T cells strongly expressed HLA-G whereas untreated control tumors were HLA-Gneg. IFN-γ stimulation of EwS cell lines in vitro induced expression of HLA-G protein. We conclude that EwS cells respond to tumor-infiltrating T cells by upregulation of HLA-G, a candidate mediator of local immune escape. Strategies that modulate HLA-G expression in the tumor microenvironment may enhance the efficacy of cellular immunotherapeutics in this cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.