| 研究実績の概要 |
We have focused on CSF1R marker, which identifies tumor associated macrophages, as well as a series of associated tumor microenvironment immune biomarkers.In this second year of research we have successfully advanced in the project. The series of cases has expanded, DLBCL (n=240) and FL (n=100) from Japan and FL Europe (n=88). Staining was successful for IL10, TFGB, CCR2, CASP3, CD14, IL17A, CD169, CD204 and RGS1, among others. In DLBCL Japan CSF1R M2-like macrophages associated with poor progression free survival (PFS) (P=0.016). High CD163 with poor overall survival (OS) and PFS (P=0.009 and P=0.005). In FL Europe: (1) High grade FL correlated with high follicular CSF1R (60.7% vs. 5.1%, P<0.0001); (2) High follicular CSF1R had trend correlation to poor OS (P=0.091); (3) High CD163 correlated with higher LDH (P=0.003); (4) COX regression between CSF1R and FLIPI showed only FLIPI significant for PFS. Atomic force microscopy identified connection area between macrophages and B-lymphocytes.In-vitro study of macrophages and FL showed increased gene expression of angiogenesis, matrix degradation of chemokine signaling; GSEA analysis showed increased markers of host immune response type II, including macrophage markers.In sinonasal DLBCL Japan, high macrophages associated to higher genomic copy number changes and RGS1 marker was identified with prognostic relevance. In summary, our results are highlighting the relevance of CSF1R and immune microenvironment biomarkers in the pathogenesis of two of the most frequent non-Hodgkin lymphomas of Western Countries as well as Japan.
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