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16.03.2019 | Original Article Open Access

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

Zeitschrift:
Cancer Immunology, Immunotherapy
Autoren:
Panagiotis Tsagozis, Martin Augsten, Yifan Zhang, Tian Li, Asle Hesla, Jonas Bergh, Felix Haglund, Nicholas P. Tobin, Monika Ehnman
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00262-019-02322-y) contains supplementary material, which is available to authorized users.

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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.

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Zusatzmaterial
Supplementary material 1 (PDF 38613 KB)
262_2019_2322_MOESM1_ESM.pdf
Literatur
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