A study led by Ludwig Lausanne’s Ping-Chih Ho and postdoctoral fellow Giusy Di Conza identified a means by which cancer cells engineer the conversion of immune cells known as macrophages from destroyers of tumors to supporters of their growth and survival. The study, published in October in Nature Immunology, showed that this transformation is triggered by β-glucosylceramide, a lipid secreted by cancer cells, and identified some of the key events that drive the pro-tumor “polarization” of tumor-associated macrophages (TAMs). Giusy, Ping-Chih and their colleagues report that β-glucosylceramide binds to a receptor named Mincle on TAMs, triggering a stress response within the endoplasmic reticulum. That stress response is partly mediated by a signaling protein named XBP1, and the researchers found that it is not only vital for TAM polarization, but also supports cancer cell survival. They also report that another signaling cascade coordinates with the one involving XBP1 to induce TAM polarization. This one involves a signaling protein named STAT3 that directly regulates the expression of genes. The findings suggest new drug targets to reprogram TAMs for cancer therapy.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).