Some types of cancer cells are surrounded by a dense layer of connective tissue that acts as a barrier to cancer-killing immune cells. That poses a problem for immunotherapies, treatments that depend on interactions between immune cells and cancer cells. But a new NCI-funded study in mouse models of metastatic breast cancer suggests that plerixafor (Mozobil)—a drug already used for bone marrow transplants—can thin this protective tissue layer and allow more immune cells to reach the tumors. The results, published January 30 in the Proceedings of the National Academy of Sciences, also show that treating mice with plerixafor improved how well immune checkpoint inhibitors, a common type of immunotherapy, worked to decrease metastasis and prolong survival. Given that immune checkpoint inhibitors don’t work well for most women with metastatic breast cancer, these findings suggest that adding plerixafor might be a way to boost the efficacy of these treatments, wrote the lead investigator, Rakesh Jain, Ph.D., of Harvard Medical School and Massachusetts General Hospital, and his colleagues. There are multiple ongoing clinical trials of plerixafor for people with different types of cancer, and a trial for people with breast cancer is being explored, Dr. Jain noted. In several of these studies, the safety of the treatment, as well as how it affects immune cells within the tumor microenvironment, will be assessed. But dense connective tissue may not be the only reason why checkpoint inhibitors are ineffective for some women with breast cancer, noted George Sledge, M.D., of Stanford University, in an accompanying commentary. Nevertheless, he wrote, “new approaches are still needed if we are to optimize checkpoint inhibitor therapy,” and the results of this study “offer a clinically testable hypothesis.” The study “touches on many different layers of complexity in cancer development and progression and how to think about targeting tumors in a more effective manner,” said Jeffrey Hildesheim, Ph.D., chief of the Tumor Biology and Microenvironment Branch of NCI’s Division of Cancer Biology, who wasn’t involved in the study.