Dataset Information

T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G.

ABSTRACT: 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-? 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.

SUBMITTER: Spurny C

PROVIDER: S-EPMC5814230 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G.

Spurny Christian C Kailayangiri Sareetha S Altvater Bianca B Jamitzky Silke S Hartmann Wolfgang W Wardelmann Eva E Ranft Andreas A Dirksen Uta U Amler Susanne S Hardes Jendrik J Fluegge Maike M Meltzer Jutta J Farwick Nicole N Greune Lea L Rossig Claudia C

Oncotarget 20171222 5

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-G<sup>pos</sup> 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 lymphocyte ...[more]

PMID: 29464090

Similar Datasets

Project description:BackgroundHigh temperature requirement A1 (HTRA1), a member of the HTRA family, is a serine peptidase involved in many crucial bioprocesses such as proliferation, mitochondrial homeostasis, apoptosis, and protein quality control. It also plays an important role in the development of various tumors. However, the potential role and mechanisms of action of HTRA1 in breast cancer (BRCA) remain unclear. We conducted a bioinformatics-based study to investigate HTRA1 expression in BRCA alongside its associations with immune-cell infiltrates and survival outcomes.MethodsThe expression of HTRA1 in BRCA samples was analyzed using RNAseq datasets from The Cancer Genome Atlas and Gene Expression Omnibus. R software was employed to assess the relationship between HTRA1 expression and clinicopathological characteristics, tumor-infiltrating immune cells, and immunity-associated biomarkers in BRCA. MethSurv and cBioPortal database were utilized to evaluate DNA methylation and genovariation within the HTRA1 DNA. Receiver operating characteristic curves, Kaplan-Meier analysis, and Cox regression were performed to estimate the impact of HTRA1 on diagnosis, prognosis, and response to chemotherapy in BRCA.ResultsHTRA1 expression was significantly downregulated in BRCA tissues compared to adjacent normal breast tissue controls. Differentially expressed genes associated with HTRA1 expression primarily enriched in cell proliferation pathways. Furthermore, altered HTRA1 expression significantly correlated with patient age, tumor histological type, T stage, progesterone receptor/estrogen receptor status, and PAM50 subtype of BRCA. Both positive and negative associations were observed between HTRA1 levels and the abundance of different types of immune cells, as well as immune biomarkers, including resting mast cells, follicular helper T cells, PD-L1, p53, and Ki67. Low HTRA1 expression was related with pathological complete response in luminal B BRCA patients undergoing chemotherapy. Additionally, lower HTRA1 expression in BRCA was associated with inferior overall survival and relapse-free survival.ConclusionsHTRA1 expression is associated with immune-cell infiltration, response to chemotherapy, and survival outcomes in BRCA. HTRA1 has the potential to serve as a promising biomarker and therapeutic target moving forward.

Dataset Information

T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G.

Publications

T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets