In Science this week, a multi-institute research team reports a study establishing that tumors with defects in a genome maintenance pathway called mismatch repair (MMR) are highly responsive to a certain type of immunotherapy. Building off of a previous study that showed colorectal cancers with MMR deficiency were sensitive to immune checkpoint blockade with anti-PD-1 antibodies, the scientists analyzed 86 patients with 12 different MMR-deficient tumor types in an ongoing clinical trial. They found that the anti-PD-1 antibody pembrolizumab controlled disease for 66 patients, with complete responses in 18 patients. The investigators estimate that this kind of immunotherapy may be effective for up to 60,000 MMR-mutant cancer cases every year in the United States, based on analysis of genome sequencing data from 12,019 cancers representing 32 distinct tumor types. GenomeWeb has more on this, here.
And in Science Translational Medicine, a group of US and Australian scientists presents data suggesting that a particularly aggressive form of chemotherapy-resistant breast cancer can be treated with immunotherapy-containing combination regimens. In their study, the team found that triple-negative breast cancers (TNBC) with defects in the DNA-repair gene BRCA1 had elevated mutation rates and were heavily infiltrated by immune cells. Although combination immunotherapies showed little effect in mouse models of BRCA1-mutate TNBC, the addition of the chemotherapeutic cisplatin to this regimen promoted tumor regression and improved survival, with no evidence of drug resistance.