Fig. 8. The synergistic effects of combined adenosinergic antagonism and CD73 blockade on tumor control is CAF-dependent.

a The progression of MC38^Cd73KO and MC38-RFP in WT mice was compared the unmodified MC38 tumors. A group of MC38^Cd73KO-bearing mice also received i.p. injection of anti-CD73 every other day. Tumor progression was examined every day. b The percentage of TIL-CD8 T cells and c IFN-γ-producing CTLs in the TME of MC38 and MC38^Cd73KO were determined via FACS and summarized. d–g The progression of MC38^Cd73KO tumors established in WT mice with MSCs co-inoculation with or without anti-CD73 or PSB1115 treatment was examined every day d. e CD73⁺ (red) and α-SMA⁺ (green) cells and their distribution within the TME of MC38^Cd73KO tumors without or with MSC co-inoculation were analyzed and quantified via IHC. f, g The percentage of CD73^hi/+ CAFs (f) and TIL-CD8 T cells (g) in the TME MC38^Cd73KO tumors co-inoculated with MSCs following different treatments were determined via FACS and summarized. h–j The progression of MC38^Cd73KO tumors co-inoculated with MSC and treated with ZM243185 and PSB1115 combination in the absence or presence of anti-CD73 was examined every day g. i, j The percentage of CD73^hi/+ CAFs i and TIL-CD8 T cells j in the TME MC38^Cd73KO tumors with MSC co-inoculation following different treatments were determined via FACS and summarized. a, d, g p values were determined via multiple t-tests where the tumor sizes at each time point were compared. b, c, e, f, i, j Error bars depict mean ± SEM. p values were determined via two-tailed unpaired Student’s t-test. All experiments were repeated at least two times. Source data are provided as a Source Data file.