Figure 7.

Col003 augments the therapeutic efficacy of anti-PD-L1 antibody in BrMs

(A) 4T1-BMT5 or LLC1-BMT5 cells were intracardially implanted into mice. Seven days after cell injection, mice were intraperitoneally injected with anti-PD-L1 antibody alone (200 μg/mouse) every third day four consecutive times or with anti-PD-L1 plus Col003 (20 mg/kg) (top). Representative BLI images of each group are shown. BLI photon fluxes in the brain for each mouse were quantified (mean ± SD, n = 8 mice for each group, two-sided Mann-Whitney test). ∗∗∗p < 0.001.

(B) The BMFS of mice was evaluated (n = 8 mice for each group, Kaplan-Meier model with two-sided log-rank test). ∗∗∗p < 0.001.

(C) Representative FACS plots and quantification of CD206⁺CD11b⁺CD45^low and CD11c⁺CD11b⁺CD45^low cells in the BrM tissues.

(D) Representative FACS plots and quantification of CD45⁺CD3⁺CD8⁺cells in the BrM tissues.

(C and D) Data are expressed as mean ± SEM of n = 5 independent experiments, Student’s t tests. ∗∗∗p < 0.001.

(E) Co-staining of GZMB and CD8α in mouse BrM tissues. Representative images are shown (left). Scale bars, 100 μm. The GZMB⁺ and CD8α⁺ positive cells in each microscope field were counted (mean ± SEM, n = 6 randomly selected fields for each group, Student’s t tests). ∗∗∗p < 0.001.

(F) Schematic diagram shows the findings revealed in this study. Upregulation of HSP47 in tumor cells promotes collagen deposition in the brain metastatic niches, which promotes M2 microglial polarization and expression of anti-inflammatory cytokines through the integrin α2β1/NF-κB pathway, resulting in repression of anti-tumor CD8⁺ T cell immunity.