Andrea Schietinger, PhD

Our immune system has special cells called T cells that can recognize and attack cancer. Even though these tumor-fighting cells are often present, many tumors still grow because T cells stop working properly during cancer development. Cancers can be grouped into two main types based on how the immune system responds. Some are called “hot” tumors. In these cancers, T cells are able to enter the tumor, but the tumor environment weakens them so they cannot kill cancer cells. Other cancers are called “cold” tumors which comprise approximately half of all human cancers. In cold tumors, T cells are mostly missing from the tumors. Cold cancers do not respond well to immune-based treatments. Scientists still do not fully understand why T cells fail to enter cold tumors or why these cancers resist treatment. To study this, we created preclinical mouse models in which tumors grow naturally and show cold immune phenotypes. Using these models, we found that tumor-fighting T cells are present in nearby lymph nodes but do not move into the tumor. Over time, these T cells become resistant to immune treatments, which is linked to the loss of important genes needed for T cell function. In this project, we will study in mice and patients with cancer why T cells get stuck, fail to enter tumors, and stop responding to treatment. This research may lead to new ways to make immunotherapy work for patients with immune-cold cancers.