Research in The American Journal of Pathology shows that blocking complement factor B suppresses cancer growth, induces tumor cellular senescence, and remodels the tumor immune microenvironment

November 9, 2026 – Researchers have identified a promising new target in the treatment of pancreatic cancer. A new study in The American Journal of Pathology, published by Elsevier, demonstrates that blocking complement factor B (CFB), a pivotal enzyme in the alternative complement pathway, halts cancer growth and alters the tumor microenvironment. The greatest tumor suppression was observed when CFB inhibition was combined with chemotherapy and immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat, in large part because of its highly immunosuppressive nature. Effective therapies are limited, and the five-year survival rate is below 15%.

The researchers of this study first examined the clinical significance of CFB in human PDAC tissues and found that high levels of the enzyme in the connective tissue surrounding the tumor were associated with poorer patient survival rates and more frequent hematogenous recurrence. They then investigated the effects of the selective CFB inhibitor iptacopan in pancreatic cancer cells and found that CFB blockade reduced cancer cell proliferation and promoted cellular senescence, accompanied by increased expression of p21, a protein that signals cancer cells to stop growing.

“Iptacopan is an already approved first-in-class oral CFB inhibitor that has shown clinical efficacy and safety in certain rare complement-mediated diseases,” explains lead investigator Shigetsugu Takano, MD, PhD, Department of General Surgery, Chiba University, Graduate School of Medicine, Japan. “In our previous research, we identified that CFB is upregulated during PDAC development. This led us to test the use of iptacopan in a mouse model of PDAC.”

Lead author Daren Zhou, MD, PhD, Department of General Surgery, Chiba University, Graduate School of Medicine, Japan, adds, “We demonstrated that iptacopan significantly suppressed tumor growth. Importantly, CFB blockade also altered the tumor immune microenvironment. We saw a decrease in regulatory T cells together with increased CD8+ T-cell infiltration, suggesting that CFB blockade was doing more than directly affecting tumor cells; it was also reshaping the immune context of the tumor. This finding led us to explore combination therapy with immune checkpoint blockades, where we observed additional antitumor activity.”

Because pancreatic cancer creates an exceptionally immunosuppressive environment, targeting the tumor cells directly via immunotherapy has had limited success. This study shows that CFB may be one of the mechanisms helping to maintain that defensive environment. CFB inhibition targets both the cancer cells and their surroundings.

Dr. Takano concludes, “Our findings support iptacopan’s potential as a combination therapy with chemotherapy and immunotherapy, although further preclinical and clinical studies are needed. We hope these findings will contribute to developing new, more effective treatments for pancreatic cancer.”