Intratumoral infection by CMV may change the tumor environment by directly interacting with tumor-associated macrophages to promote cancer immunity.

Cytomegalovirus (CMV) is a herpesvirus that induces an extremely robust and sustained immune response. For this reason, CMV has been proposed as a vaccine vector to promote immunity to both pathogens and cancer. However, exploration of CMV as a vaccine vector is at an early stage and there are many questions. Using a mouse melanoma model, we recently found that a CMV-based vaccine induced large populations of melanoma-specific T cells, but was not effective at slowing tumor growth unless it was injected directly into the tumor. These surprising results have led us to hypothesize that CMV may be adept at modulating the tumor micro-environment through its infection of macrophages. Importantly, injection of CMV into the growing tumor synergized with blockade of the PD-1 checkpoint to clear well-established tumors. Here, we discuss our results in the context of CMV-based vaccines for pathogens and cancer.