Many tumors are surrounded by immune cells called tumor-associated macrophages (TAMs), which often help cancers grow, spread, and evade the immune system. These macrophages can block T cells from entering tumors and contribute to resistance against immunotherapy. While TAMS have long been recognized as an important target, current therapies have been unable to effectively eliminate these harmful cells.
Dr. Guerriero’s laboratory has identified a group of TAMs expressing a molecule called TREM2. These macrophages are found across many solid tumors but are largely absent from normal tissues, making them an attractive therapeutic target. To attack these cells, Dr. Guerriero has developed an innovative strategy that engineers a patient’s own monocytes — immune cells that naturally enter tumors — with a chimeric antigen receptor (CAR). These engineered monocytes are designed to recognize and eliminate TREM2-positive macrophages inside tumors.
Early studies in mice have already shown promising results, including tumor shrinkage, improved survival, and stronger T cell activation. This project will focus on confirming safety and effectiveness, improving the engineered cells by adding immune-stimulating cytokines, and developing a clinical-grade product suitable for patient testing. This work could establish an entirely new form of cellular immunotherapy aimed not at cancer cells directly, but at dismantling the tumor’s protective immune environment and restoring the body’s ability to fight cancer.
Research Focus
Breast Cancer, Lung Cancer, Pancreatic Cancer
Projects and Grants
Turning the innate immune system against itself: CAR-monocytes targeting tumor macrophages
