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. 2019 Sep 12;11(10):e10576. doi: 10.15252/emmm.201910576

Figure 8. The IL‐6 signaling complex is of diagnostic relevance and a therapeutic target in IL‐6R+ DLBCL .

Figure 8

  • A–D
    Frequency of STAT3 phosphorylation (A), and overall as well as disease‐specific survival probability (B), and of overall and disease‐specific mortality of DLBCL patients stratified according to subtype and disease stage (C and D). Of all 814 evaluable patients, 367 were classified as GCB and 376 were classified as non‐GCB/ABC‐DLBCL according to the Hans algorithm. Phospho‐STAT3 positivity was defined as expression in ≥ 17% of tumor cells and more commonly found in ABC‐DLBCL tumors, and in more advanced (stage 3 and 4, relative to stage 1 and 2) disease (A). p‐STAT3 positivity was a strong negative prognostic factor in the entire cohort (B) and associated with higher overall as well as disease‐specific mortality in both ABC‐ and GCB‐DLBCL subtypes (C and D).
  • E–H
    Effect of IL‐6R neutralization by twice‐weekly injection of 250 μg/dose of tocilizumab or an isotype control antibody, starting 2 weeks after tumor cell injection, on (E and F) the spleen weights of MISTRG6 mice transplanted with 1 × 106 primary DLBCL cells (expanded by one serial passage through MISTRG6 mice), on the bone marrow lymphoma burden of OCI‐Ly3‐transplanted MISTRG mice (G), and on the splenic lymphoma burden of RC‐K8‐transplanted MISTRG6 mice (H), all assessed at around 4 (G and H) to 8 (E) weeks after tumor cell injection. Representative microscopy images in (F) show STAT3 phosphorylation in spleen‐colonizing primary cells exposed to either tocilizumab or isotype control antibody (in brown, counterstained in blue with hematoxylin), and an H&E‐stained section from the same mouse. TCZ, tocilizumab. Scale bars, 100 μm.
Data information: Results in (E, G, and H) are pooled from two (E and G) or three (H) independent studies each. Horizontal lines indicate medians. P‐values were calculated by the chi‐square test (A, C, D), by log‐rank test (B), or by the Mann–Whitney test (E, G, H). n is indicated in the figure panels throughout.Source data are available online for this figure.