Response to PD-1 inhibition in MMRd/MSS pancreatic ductal adenocarcinoma: the relevance of parallel testing

While pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, a small fraction of patients show high microsatellite instability (MSI-H) and may respond to immune checkpoint inhibition. An MSI-H genotype is usually associated with deficiencies in the DNA mismatch-repair mechanism (MMRd). However, discordances between the mismatch-repair status by immunohistochemistry and the microsatellite status by molecular analyses have been noted. To date it is not clear whether PDAC patients with mutations in mismatch repair genes, which result in loss of protein expression (MMRd), who nonetheless retain microsatellite stability (MSS), can profit from checkpoint inhibitor therapy. Here, we present the case of a PDAC patient, diagnosed as MMRd/MSS, who responded to checkpoint inhibitor therapy after failing two lines of chemotherapy. Our data suggest that both MMR and microsatellite status should be determined in PDAC patients and that MMRd status alone, even in an MSS phenotype, can constitute an indication for checkpoint inhibitor therapy.