Web Analytics Made Easy - StatCounter

News : Glycoprotein Revealed to Be a Barrier against Cancer Immunotherapy


T lymphocytes and cancer cell

 

Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in calcium/phosphate homeostasis, which regulates various cellular processes in normal development and tumorigenesis. After analyzing more than 1,000 genes, researchers from the University of Michigan (U-M) Rogel Cancer Center found that this glycoprotein may also serve as a barrier to cancer immunotherapy.

Their findings are published in the journal Cancer Cell in a paper titled, “Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance.”

“We believe STC1 is a checkpoint inside the cell. It’s an eat-me blocker—it blocks macrophages and dendritic cells to eat dying or dead cancer cells. We think that if we can target the STC1 pathway, it would release the blocked eat-me signal,” explained study senior author Weiping Zou, MD, PhD, the Charles B. de Nancrede professor of pathology, immunology, biology, and surgery at the University of Michigan.

The researchers were drawn to STC1 due to its limited understanding of what role it plays in cancer.

“Immunotherapy induces durable clinical responses in a fraction of patients with cancer. However, therapeutic resistance poses a major challenge to current immunotherapies. Here, we identify that expression of tumor stanniocalcin 1 (STC1) correlates with immunotherapy efficacy and is negatively associated with patient survival across diverse cancer types,” the researchers wrote.

The researchers first demonstrated that STC1 was linked with low activation of T cells and worse survival in melanoma patients treated with immunotherapy. They checked against the Cancer Genome Atlas database and found high levels of STC1 tied to worse survival in 10 different cancer types.

The researchers then used mouse models to show that STC1 within tumors was decreasing the anti-tumor T-cell response by impairing the antigen-presenting cells. Tumor STC1 was found to stop the process of macrophages. Specifically, the tumor STC1 was found to trap a key eat-me signal called calreticulin (CRT). Without sufficient surface CRT, the macrophages won’t efficiently eat the dead tumor cells.

This finding suggests that targeting the interaction between STC1 and CRT might be a pathway toward making immunotherapy more effective.

“What we are talking about is before anything has happened. Before the T cells were activated, the tumors have already implemented strategies so they cannot be captured. This may be why some patients are resistant to immunotherapy: their tumors express too much STC1. When you block the eat-me signal, the antigen-presenting cells cannot do their job,” Zou said.

Targeting the STC1 and CRT interaction inside the cell is trickier than if it were on the cell surface. The researchers are currently investigating whether they can develop a small compound that would penetrate the cell and interfere with the STC1-CRT interaction.

Recent Posts