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Open Access 01-06-2019 | Soft Tissue Sarcoma | Original Article

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

Authors: Panagiotis Tsagozis, Martin Augsten, Yifan Zhang, Tian Li, Asle Hesla, Jonas Bergh, Felix Haglund, Nicholas P. Tobin, Monika Ehnman

Published in: Cancer Immunology, Immunotherapy | Issue 6/2019

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 IL10^low, PTGS2^low or CD163^low 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.

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Title: An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma
Authors: Panagiotis Tsagozis
Martin Augsten
Yifan Zhang
Tian Li
Asle Hesla
Jonas Bergh
Felix Haglund
Nicholas P. Tobin
Monika Ehnman
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keywords: Soft Tissue Sarcoma
Sarcoma
Published in: Cancer Immunology, Immunotherapy / Issue 6/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02322-y

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Abstract

Background

Methods

Results

Conclusions

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