Figure 5. CXCL10-chemokine expression in orthotopic mouse model has anti-tumoral effect.

(A) Rectal tumors derived from orthotopically implanted control CT26 cells in immuno-competent isogenic host (left, rectum opened longitudinally), or in immuno-deficient host (right). Arrows denote tumor situs, arrowheads normal rectum. Size bar: 5 mm. (B) HE staining, poorly differentiated invasive adenocarcinoma, derived from CT26-control cells in isogenic host. Size bar: 50 μM. (C) Enlargement, spindle-shaped infiltration of muscularis. (D) Tumor derived from CT26-control cells in Rag1^-/- host, note vascularisation (arrow). (E) Tumor derived from CT26-CXCL10 cells in Rag1^-/- host, featuring necrosis. Size bar, 20 μM. (F) In immune-deficient Rag1-/- hosts, blood vessel density is significantly lower in tumors derived from CXCL10-expressing clones as compared to CT26 control clones. Cryosections were stained with anti-van-Willebrand-factor antibody for n=3 tumors each for both group, and ten high-power fields were quantified by ImageJ software. (G) Schematic summary on the role of CXCL9-11 in tumorigenesis. Left side: high intratumoral expression of CXCL9-11 inhibits blood vessel formation and attracts CTLs and T_H1 cells, expressing the chemokine receptor CXCR3, leading to tumor regression. Right side: patients with low intratumoral chemokine expression lack beneficial T-cell infiltration, leading to unimpeded tumor growth and metastasis formation.