Combining Innate Immunity With Radiation Therapy for Cancer Treatment

The widely shared goal of cancer immunotherapy is to stimulate an immune response of sufficient quality and magnitude to destroy primary malignancies and their metastases. Cancer immunotherapy has taken many cues from the development of successful antimicrobial vaccines.

Antimicrobial vaccines rely on the immune system’s capacity to distinguish self-tissues from infectious non-self so that invading pathogens, and the cells they might infect, could be efficiently identified and eliminated, while sparing healthy tissues. The process of discriminating self from infectious non-self is facilitated by the millions (and in some cases billions) of years of evolutionary divergence that separates vertebrates from the pathogens that infect them.

This separation has given rise to individual proteins and other generalized molecular structures that serve to distinguish microbes from men. In theory, malignant cells that express protein antigens that either are unique to the tumor, vastly over-expressed by the tumor, or whose expression is at least restricted to a narrow range of self-tissues provides a potential immunologic handle whereby tumors may be specifically recognized and destroyed.

In practice, however, it has proven unexpectedly difficult to coax the immune system into vigorously rejecting malignancies, despite repeated demonstrations that tumor-associated antigens can provoke immune responses. In this issue of Clinical Cancer Research, Mason et al. (1) shows, using a murine subcutaneous and lung metastasis sarcomatreatment model, that synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (characteristic of bacterial DNA) could be given with conventional radiation therapy to greatly augment therapeutic efficacy through an apparent immune-mediated.