Many patients with triple-negative breast cancer (TNBC) do not respond to combination treatment with chemotherapy and immunotherapy. Understanding what makes these tumors immunologically “cold,” or resistant to therapy, and how to turn them immunologically “hot,” could improve patient outcomes.
Researchers led by Xi Chen, Ph.D., identified one such mechanism in which cancer cells can evade the immune system via an ancient stress sensor IRE1α activation, which blocks pathways that would normally ignite “cold” tumors and initiate an immune response. Using an IRE1α-selective inhibitor, ORIN1001, the researchers reversed these effects and prompted a robust immune response in vivo in combination with taxane-based chemotherapy, effectively converting the immunologically “cold” tumors to “hot” tumors. These results highlight IRE1α as a potential therapeutic target to overcome treatment resistance in patients with TNBC.