Case Report: Immune and Genomic Characteristics Associated With Hyperprogression in a Patient With Metastatic Deficient Mismatch Repair Gastrointestinal Cancer Treated With Anti-PD-1 Antibody

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status of tumors is a distinct predictive biomarker of immune checkpoint inhibitors (ICIs) for colorectal and non-colorectal cancer populations. The overall response rate (ORR) varies from approximately 40% to 60%, indicating that nearly half of MSI-H tumors do not respond to ICIs. The mechanism of response heterogeneity in MSI-H/dMMR cancers is unclear. Some patients who have been treated with ICIs have developed a novel pattern of progression called hyperprogression, which is defined as unexpected accelerated tumor growth. No case of MSI-H/dMMR immunotherapy-associated hyperprogression has been reported in the literature. Here, we present the case of a patient with dMMR gastrointestinal cancer who suffered hyperprogressive disease (HPD) after treatment with nivolumab. We explored the potential mechanisms of HPD by clinical, immune, and genomic characteristics. Extremely high levels of serum LDH, low TMB and TILs, and the disruption of TGFβ signaling, may be related to hyperprogression.