Issues

The cover image shows the structure of pembrolizumab, a well-known immune checkpoint inhibitor used widely in treatment of certain advanced cancers, where it sometimes provides dramatic clinical benefit. In this issue, a case report (beginning on page 351) by Mancuso and colleagues provides justification for further study of checkpoint inhibitors in the context of cancer prevention, as distinct from treatment. A patient with Muir—Torre syndrome, a DNA repair deficiency, was observed to regularly develop many neoplastic and hyperplastic lesions during follow up over many years. After he received pembrolizumab for treatment of his bladder cancer, not only did he achieve a complete response, but new lesions stopped appearing. While a case report cannot be used to prove or disprove a hypothesis, it is possible that at least for patients with DNA repair deficits, and perhaps more generally, immune checkpoint blockade may allow “immune-interception” of clinically undetectable neoplastic lesions, accounting for the unexpected lack of new neoplasms in this patient. Clinical trials of “immunoprevention” will be challenging, but there is a clear rationale for work in this area, both in the lab and the clinic.