Remarkable Responses to Checkpoint Blockade in Solid Tumors of Many Types

Mutations in genes that repair DNA damage are seen in >5% of common solid tumors. These “mismatch-repair” mutations are presumed to contribute to oncogenesis, and they generate many neoantigens that should be recognized as “foreign” by the immune system. However, immune attack is thwarted by a “checkpoint” molecule (PD-1) that is produced by tumor cells.

A U.S.-based team previously found that colon cancers with mismatch-repair mutations often respond to “checkpoint-inhibitor” drugs that block PD-1 — or its T-cell receptor (PD-L1; NEJM JW Gen Med Jun 16 2015; [e-pub] and Science 2015; 348:62). They now report a study of 86 consecutive patients who had 12 different types of solid tumors with mismatch-repair mutations and progressive disease d…