Gene expression profile at single cell level of syngeneic ovarian tumors from mice treated with inhibitory Activin-A antibody or control IgG
Effective targeting of cancer-associated fibroblasts (CAFs) is hindered by the lack of specific biomarkers and a poor understanding of the mechanisms by which different populations of CAFs contribute to cancer progression. While the role of TGFß in CAFs is well-studied, less attention has been focused on a structurally and functionally similar protein, Activin A (encoded by INHBA), which is typically associated with poor survival and advanced stage in ovarian cancer. Here, we identified INHBA(+) CAFs as key players in tumor promotion and immune evasion. In syngeneic ovarian cancer mouse models, intraperitoneal injection of the Activin A neutralizing antibody attenuated tumor progression and infiltration with the host INHBA(+) CAFs and M2 macrophages. Collectively, our study identified an INHBA(+) subset of pro-tumoral CAFs as a potential therapeutic target in ovarian cancer. Overall design: To facilitate uniform recruitment of host fibroblasts to the tumor, we used the peritoneal abrasion-facilitated C57BL/6 p53/myc/Hras model in which peritoneal wound healing facilitates the recruitment of fibroblasts into the tumor. C57BL/6 mice with peritoneal abrasion were injected i.p. with syngeneic p53/myc/Hras ovarian cancer cells (genotype: p53-/-, myc, Hras). One day after cancer cell injection, the mice received daily i.p. injections of the Activin A neutralizing antibody (n=8) or control IgG (n=7).  After 10 days of treatment, mice were euthanized to assess the intraperitoneal tumor burden. Mice treated with the Activin A neutralizing antibody had smaller tumor lesions at the site of peritoneal abrasion.