Fig 2: Immunofluorescence staining of cryosections obtained from mock-infected and NCC brain samples for chemokines. Immunofluorescence staining (IF) of cryosections obtained from mock-infected (A1 & B1) and 3 wks p.i. NCC brain (A2–A4 & B2–B4) sections. Chemokine CCL5, CCL9 are shown in red color, CD31, an endothelial cell marker is shown in green color and DAPI representing nuclear staining is shown in blue color. (A1–A4) CCL5 expression in endothelial cells (A1) Mock sample (IF+DIC, 40 X). (A2) Infected sample (IF+DIC, 40x). (A3) CCL5 IF with DIC. (A4) CCL5 with CD31 IF. (B1–B4) CCL9 expression in endothelial cells. (B1) Mock (IF+DIC, 40 X). (B2) Infected sample (IF+DIC, 40x). (B3) CCL9 IF with DIC. (B4) CCL9 with CD31 IF.

Fig 3: Myc Instructs Stromal Changes in Lung Adenomas, Related to Figures 2, 3, 4, and 7Schematic representation of Myc-induced stromal changes in lung adenocarcinoma. Activation of deregulated Myc in epithelial KRasG12D-driven lung adenoma cells rapidly leads to efflux of B, T and NK lymphocytes and recruitment of macrophages. Myc-induced IL-23 promotes efflux of B, T and NK cells whereas Myc-dependent CCL9 recruits macrophages. The macrophages stimulate angiogenesis via overt VEGF production and repel T cells via surface expression of PD-L1. Myc-dependent tumor progression requires IL-23 and CCL9 signaling to NK cells and macrophages, respectively. De-activation of deregulated Myc in established KRasG12D-Myc adenocarcinomas leads to the rapid reversal of these stromal changes, tumor cell death and regression.

Fig 4: Pharmacological modulation of chemokines from MIP-1 family (CCL3 and CCL9) via neutralizing antibodies and their receptors (CCR1 by J113863, CCR5 by TAK-220 or AZD -5672) reduces neuropathic pain symptoms and influences morphine analgesia—evidence from mice model evoked by chronic constriction injury of the sciatic nerve.

Fig 5: Time-dependent changes in the mRNA levels of CCL3 (A), CCL4 (C), and CCL9 (E) measured via RT-qPCR and changes in the protein levels of CCL3 (B), CCL4 (D), and CCL9 (F) measured using ELISA in the spinal cord of naive and CCI-exposed mice (from 1 to 35 days). The data are presented as the mean fold changes relative to the control ± SEM (n = 4–10). The results were evaluated using one-way ANOVA followed by Bonferroni’s post hoc test for comparisons of selected pairs. * p < 0.05, ** p < 0.01, and *** p < 0.001 indicate significant differences vs. the naive group. Abbreviations: -: naive; CCI: chronic constriction injury of the sciatic nerve.