Tumor β-Catenin Expression Associated With Poor Prognosis to Anti-PD-1 Antibody Monotherapy in Non-small Cell Lung Cancer

Background/aim: Tumor intrinsic β-catenin signaling has been reported to influence the tumor immune microenvironment and may be a resistance mechanism to immune checkpoint inhibitors in various cancers.

Patients and methods: We studied the association between tumor β-catenin expression and survival in 50 patients with non-small cell lung cancer (NSCLC) treated with anti-programmed death-1 antibody monotherapy. Tumor β-catenin expression was evaluated by immunohistochemistry.

Results: Patients with positive tumor β-catenin expression (20% of all patients) had worse progression-free survival and overall survival compared with those with negative tumor β-catenin expression. Patients with positive tumor β-catenin expression had reduced CD8⁺ cell and CD11c⁺ cell infiltration into tumor nests than those with negative tumor β-catenin expression. RT-PCR of tumor tissue revealed that patients with positive tumor β-catenin expression showed lower gene expression of CD8A, CD4, IFN-γ, BATF3, and CCL4. Knockdown of CTNNB1 tended to increase CCL4 expression, likely mediated by ATF3, in a lung cancer cell line with positive β-catenin expression.

Conclusion: NSCLC patients with positive tumor β-catenin expression that were treated with anti-programmed death-1 antibody monotherapy had poor prognosis.