Fig. 10. Compound 182 does not promote systemic inflammation and autoimmunity.

a–c AT3-OVA mammary tumor cells were implanted into the fourth inguinal mammary fat pads of 8-week-old C57BL/6 female mice. Mice were treated with Compound 182 (CMP-182; 10 mg/kg i.v.; n = 8) or saline (n = 8) on days 6, 8, 10, 12, 14, 16, 18, and 21 after tumor cell implantation. a Serum cytokines were determined by flow cytometry using a BD Cytokine Bead Array (BD Biosciences. b Livers, lungs, salivary glands, and colons were fixed in formalin and processed for histological assessment (hematoxylin and eosin: H&E). Livers were also processed for Sirius Red staining. c Serum anti-nuclear antibodies (ANA) and serum liver enzymes AST and ALT in CMP-182-treated mice. d–h AT3-OVA mammary tumor cells were implanted into the fourth inguinal mammary fat pads of Mx1-Cre;Ptpn2^fl/fl mice. Mice were treated with poly I:C (250 μg/kg i.v.) to inducible delete PTPN2 on day 7, 9, and 11 after tumor cell implantation; the resultant tumor growth curves are shown in Fig. 6a. d Gross phenotype of Mx1-Cre;Ptpn2^fl/fl mice. e Spleen weight (n = 9-11 per group) and splenic CD44^hiCD62L^lo CD8⁺ and CD4⁺ effector/memory (EM) T cells and inflammatory monocytes in Mx1-Cre;Ptpn2^fl/fl (n = 6-8 per group) mice. f Serum cytokines in Mx1-Cre;Ptpn2^fl/fl mice (n = 10 per group) were determined by flow cytometry using a BD Cytokine Bead Array (BD Biosciences). g Serum liver enzymes AST and ALT in Mx1-Cre;Ptpn2^fl/fl mice (n = 10 per group). h Livers from Mx1-Cre;Ptpn2^fl/fl mice were fixed in formalin and processed for histological assessment (hematoxylin and eosin: H&E; Sirius Red). In (a, c, e–g) representative results (means ± SEM) from at least two independent experiments are shown. In (b and h) micrographs are representative of tissues from at least 5 mice per group. Significances were determined using a 2-tailed Mann–Whitney U Test.