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An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma.

ABSTRACT: BACKGROUND:Immune cells can regulate disease progression and response to treatment in multiple tumor types, but their activities in human soft tissue sarcoma are poorly characterized. METHODS:Marker-defined immune cell subsets were characterized from a tumor microenvironmental perspective in two independent cohorts of human soft tissue sarcoma by multiplex IHC, quantitative PCR and/or bioinformatics. RESULTS:B cell profiling revealed a prognostic role for CD20 protein (cohort 1, 33 patients) and MS4A1 gene expression (cohort 2, 265 patients). Multiplex IHC and gene correlation analysis supported a role in antigen presentation, immune cell differentiation and T cell activation. The prognostic role of MS4A1 expressing B cells was only observed in an IL10low, PTGS2low or CD163low tumor microenvironment according to the transcriptomic data. IL10 levels consistently correlated with the M2-like macrophage marker CD163, which also defined the majority of macrophages. A polarization of these cells toward a pro-tumoral phenotype was further supported by lack of correlation between CD163 and M1 markers like NOS2, as well as by low abundance of CD80 positive cells in tissue. CONCLUSIONS:Analysis of CD20/MS4A1 expression in soft tissue sarcoma merits further attention as a promising candidate prognostic tool for survival, but not in patients with a pronounced immunosuppressive tumor microenvironment. Macrophages are ubiquitous and polarized toward a protumoral phenotype. This provides a rationale for further studies on B cell function and immunotherapy targeting M2-polarized macrophages.

SUBMITTER: Tsagozis P

PROVIDER: S-EPMC6529392 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma.

Tsagozis Panagiotis P Augsten Martin M Zhang Yifan Y Li Tian T Hesla Asle A Bergh Jonas J Haglund Felix F Tobin Nicholas P NP Ehnman Monika M

Cancer immunology, immunotherapy : CII 20190316 6

<h4>Background</h4>Immune cells can regulate disease progression and response to treatment in multiple tumor types, but their activities in human soft tissue sarcoma are poorly characterized.<h4>Methods</h4>Marker-defined immune cell subsets were characterized from a tumor microenvironmental perspective in two independent cohorts of human soft tissue sarcoma by multiplex IHC, quantitative PCR and/or bioinformatics.<h4>Results</h4>B cell profiling revealed a prognostic role for CD20 protein (coho ...[more]

PMID: 30879106

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Project description:BackgroundSoft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators.ObjectiveThe objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas.MethodsClinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells.ResultsUnsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells.ConclusionIn summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS.

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An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma.

Publications

An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma.

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