Overcoming Beta-Catenin Signaling May Improve Immunotherapy for Melanoma

Share this content:
Metastatic melanoma tumors shield themselves from T cells by producing high levels of beta-catenin.
Metastatic melanoma tumors shield themselves from T cells by producing high levels of beta-catenin.

Researchers from the University of Chicago in Illinois have found that metastatic melanoma tumors shield themselves from T cells by producing high levels of beta-catenin, and that beta-catenin prevents T cell invasion and ultimately undermines immunotherapy, a new study published in the journal Nature has shown.

For the study, researchers analyzed tumor tissue samples from nearly 200 patients with melanoma to identify variations in their internal messaging.

Results showed that 49% of the tumors that blocked T cell infiltration had increased levels of beta-catenin signaling. In mouse models, researchers found that tumors with high levels of beta-catenin lacked CD103+ dendritic cells.

When the researchers tested two checkpoint inhibitors in the mice, they found that tumors with beta-catenin did not respond to treatment, which suggests that "the major immunologic defect in the context of melanomas expressing tumor-intrinsic beta-catenin-signaling is defective recruitment of CD103+ dendritic cells," said study author Thomas Gajewski, MD, PhD, professor of medicine and pathology at the University of Chicago.

"This is the first identified cell-intrinsic cancer-causing pathway that disrupts T cell infiltration in melanoma," Gajewski said.

RELATED: Pembrolizumab May Be More Effective, Safer Than Ipilimumab for Advanced Melanoma

"This pathway enables multiple tumor types to evade immune surveillance. Developing strategies to inhibit this signaling within tumor cells could help restore T cell access and enhance the potential of immune-mediated cancer treatment."

Recent studies have shown that approximately one-third of patients treated with checkpoint inhibitors respond to therapy.


  1. Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signaling prevents anti-tumour immunity. Nature. 2015. [Epub ahead of print]. doi: 10.1038/nature/14404.

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs