Fig 2: Effect of B. burgdorferi infection on the human immune system in humanized mice.Shown is the effect of B. burgdorferi infection on the abundance (percentage of all human CD45+ cells) and activation status (CD69 expression) of human CD19+ B cells (A-C), CD33+ myeloid cells (D-F), CD4+ T cells (G-I), and CD8+ T cells (J-L) in the peripheral blood (PBL), spleen, and left and right joints 38 days after infection. Representative FACS plots showing the mean fluorescence intensity (MFI) of CD69 expression on B cells (B), myeloid cells (E), CD4 T cells (H) and CD8 T cells (K) are presented. Depicted are box and whisker plots including all data points. The line in the box indicates the median, the upper and lower border of the box indicates the 25th and 75th percentile of the data points. Whiskers extend to minimum and maximum data points. One representative out of three independent experiments with four mice per group is shown.

Fig 3: Pharmacologic targeting of the Kyn–HTR1B–SAA–IDO1 axis in PDXs. A, Survival curve comparing vehicle (n = 26) and epacadostat-treated mice (n = 18 for 0.8 g/kg and n = 13 for 1.6 g/kg). Kaplan–Meier curve with P value of log-rank (Mantel–Cox) test. SAA3 (B) and Kyn/tryptophan (Trp) ratio (C) serum levels in NSGS mice transplanted with CD34+ healthy cells (n = 11) or with patient-derived AML cells (n = 27). D, Schematic describing pharmacologic targeting of IDO1 (epacadostat) in patient-derived AML xenograft (PDX) in NSGS mice. E, Kyn/Trp ratio in serum of PDX mice 5 weeks after AML transplant and 2 weeks after epacadostat treatment (n = 8 vehicle; n = 10 epacadostat). F, Representative flow cytometry plots depicting the percentage of human or mouse CD45+ cells in the BM of PDX mice (left) and AML burden in the BM of PDX mice at harvest (right; n = 8 vehicle; n = 10 epacadostat). G, Representative flow cytometry plots (left) and cell-cycle analysis of leukemic blasts (CD45+ CD33+) of PDX mice treated with either vehicle (n = 8) or epacadostat (Epac; n = 8). H, Cell-cycle analysis of mice in G. I, Schematic diagram showing the in vivo PDX mouse model treated with the combination therapy (Ara-C 60 mg/kg 1–5 days + epacadostat 1.6 g/kg ad libitum 3 weeks). AML burden in BM (J) and SP (K) 11 weeks after transplant, three weeks after combination therapy; control chow (ctrl; n = 4), Ara-C (n = 3), epacadostat (n = 4), and combination therapy (Ara-C + epacadostat, n = 3); one-way ANOVA; unpaired t test P values are shown for BM ctrl versus Ara-C and epacadostat groups. L, Schematic model of the Kyn–HTR1B–SAA–IDO1 axis depicting the AML-mediated osteoblastic self-reinforcing niche remodeling. All data expressed as mean ± SEM. Statistical analysis done with unpaired t test unless otherwise stated. *, P = 0.05; **, P = 0.01; ****, P = 0.0001. See also Supplementary Fig. S6. Hg, hemoglobin; PLT, platelets.

Fig 4: CeNT-treated hematopoietic stem cells successfully engraft in mice. In the CeNT GFP condition, only GFP+ cells were sorted and transplanted. (A) Outline of experiment. Percentage of human CD45+ cells 4 mo posttransplantation in (B) peripheral blood and (C) bone marrow (n = 3 to 4; **P < 0.005). (D) Representative FACS plots showing the frequency of human CD45+ cells in mouse bone marrow 4 mo posttransplantation. (E) Percentage of lymphoid (CD19+ B cells and CD3+ T cells) and myeloid (CD33+) cells within the human CD45+ population in the mouse bone marrow.

Fig 5: The expansion and activation of MDSCs in patients with MALT lymphoma. (A) The proportion of myeloid-derived suppressor cells (MDSCs) in CD45+ peripheral blood mononuclear cells (PBMCs) is higher in newly diagnosed mucosa-associated lymphoid tissue (MALT) lymphoma patients (n = 8) compared to age-matched controls (n = 12); **P < 0.01. (B) Representative flow cytometric dot plots showing MDSCs in the peripheral blood of a patient and age-matched healthy individual. (C) Representative immunofluorescence images of CD11b+CD33+ MDSCs in gastric MALT lymphoma and paired normal tissues. Red, CD11b; green, CD33; and blue, 4' ,6-diamidino-2-phenylindole (DAPI); original magnification, 400×. (D) Quantitative analysis of MDSCs (CD11b+CD33+) in gastric MALT lymphoma and paired normal tissues; **P < 0.01. (E) Representative immunohistochemistry (IHC) images of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) in gastric MALT lymphoma and paired normal tissues. Original magnification, 400×. (F) Histoscores of Arg-1 and iNOS were higher in gastric MALT lymphoma tissues compared to control; **P < 0.01, *P < 0.05.