Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 68, Issue 6, Pages 927-936Publisher
SPRINGER
DOI: 10.1007/s00262-019-02322-y
Keywords
Sarcoma; CD20; MS4A1; IL10; M2 macrophages; Prognostic marker
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Funding
- Alex and Eva Wallstrom Foundation
- Mary Beve Childhood Cancer Foundation
- Swedish Childhood Cancer Fund
- Tornspiran Foundation
- Breast Cancer Theme Center (BRECT)
- Swedish Cancer Society
- Cancer Society in Stockholm
- King Gustaf V Jubilee Foundation
- Swedish Breast Cancer Association (BRO)
- Swedish Research Council
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BackgroundImmune cells can regulate disease progression and response to treatment in multiple tumor types, but their activities in human soft tissue sarcoma are poorlycharacterized.MethodsMarker-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.ResultsB cell profiling revealed a prognostic role forCD20 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.ConclusionsAnalysis 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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