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. 2019 Jun;68(6):927-936.
doi: 10.1007/s00262-019-02322-y. Epub 2019 Mar 16.

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

Panagiotis Tsagozis  1   2 , Martin Augsten  3   4 , Yifan Zhang  3 , Tian Li  3 , Asle Hesla  1   2 , Jonas Bergh  5 , Felix Haglund  3 , Nicholas P Tobin  3 , Monika Ehnman  6
Affiliations

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

Panagiotis Tsagozis et al. Cancer Immunol Immunother. 2019 Jun.

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.

Keywords: CD20; IL10; M2 macrophages; MS4A1; Prognostic marker; Sarcoma.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Tumor-associated macrophages outnumber lymphocyte subsets in STS. a Multiplex IHC using the pan-macrophage marker CD68 (blue, left), the B cell marker CD20 (brown, left), the M1-like associated marker CD80 (blue, right) and the M2-associated marker CD163 (red, right). b Immunostaining for CD8 (brown, left) and FOXP3 (brown, right). c Immunostaining for B cells using antibodies targeting CD20, PAX5 and CD19 (brown, Htx as counterstain, tonsil as positive control)
Fig. 2
Fig. 2
CD20/MS4A1 expression is prognostic, but only in IL10low and PTGS2low tumors. a Kaplan–Meier analysis illustrating the association between CD20 B cell-positive tumors and improved metastasis-free survival (left) and overall survival (right) in the Karolinska STS cohort. b Kaplan–Meier analysis illustrating the association between MS4A1 expression and improved overall survival in the SARC STS cohort. c Kaplan–Meier analysis of CD19 expression and overall survival in the SARC STS cohort (right). d Kaplan–Meier analyses illustrating the prognostic impact of MS4A1 expression in IL10low tumors (top left), IL10high tumors (top right), PTGS2low tumors (bottom left) and PTGS2high tumors (bottom right) in the SARC STS cohort
See this image and copyright information in PMC

References

    1. Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res. 2010;316(8):1324–1331. doi: 10.1016/j.yexcr.2010.02.045. - DOI - PubMed
    1. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014–1022. doi: 10.1038/ni.2703. - DOI - PMC - PubMed
    1. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–867. doi: 10.1038/nature01322. - DOI - PMC - PubMed
    1. Nagorsen D, Scheibenbogen C, Marincola FM, Letsch A, Keilholz U. Natural T cell immunity against cancer. Clin Cancer Res. 2003;9(12):4296–4303. - PubMed
    1. Budczies J, Mechtersheimer G, Denkert C, Klauschen F, Mughal SS, Chudasama P, Bockmayr M, Johrens K, Endris V, Lier A, Lasitschka F, Penzel R, Dietel M, Brors B, Groschel S, Glimm H, Schirmacher P, Renner M, Frohling S, Stenzinger A. PD-L1 (CD274) copy number gain, expression, and immune cell infiltration as candidate predictors for response to immune checkpoint inhibitors in soft-tissue sarcoma. Oncoimmunology. 2017;6(3):e1279777. doi: 10.1080/2162402X.2017.1279777. - DOI - PMC - PubMed

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