Current Strategy to Treat Immunogenic Gastrointestinal Cancers: Perspectives for a New Era

卷:12

Review

关键词: TUMOR MUTATIONAL BURDEN;    MISMATCH REPAIR-DEFICIENT;    NIVOLUMAB PLUS IPILIMUMAB;    MICROSATELLITE INSTABILITY;    COLORECTAL-CANCER;    OPEN-LABEL;    COLON-CANCER;    TGF-BETA;    GASTROESOPHAGEAL JUNCTION;    GASTRIC-CANCER;   

DOI  :  10.3390/cells12071049

来源: SCIE

【 摘 要 】

Since pembrolizumab, an anti-programmed death-1 (PD-1) antibody, showed a dramatic response to immunogenic cancers with microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) in the pilot clinical trial KEYNOTE-016, subsequent studies have confirmed durable responses of anti-PD-1 inhibitors for MSI-H/dMMR solid tumors. As immunotherapy is described as a game changer, the therapeutic landscape for MSI-H/dMMR solid tumors including gastrointestinal cancers has changed considerably in the last decade. An MSI/MMR status has been established as the predictive biomarker for immune checkpoint blockades, playing an indispensable role in the clinical practice of patients with MSI-H/dMMR tumors. Immunotherapy is also now investigated for locally advanced MSI-H/dMMR gastrointestinal cancers. Despite this great success, a few populations with MSI-H/dMMR gastrointestinal cancers do not respond to immunotherapy, possibly due to the existence of intrinsic or acquired resistance mechanisms. Clarifying the underlying mechanisms of resistance remains a future task, whereas attempts to overcome resistance and improve the efficacy of immunotherapy are currently ongoing. Herein, we review recent clinical trials with special attention to MSI-H/dMMR gastrointestinal cancers together with basic/translational findings, which provide their rationale, and discuss perspectives for the further therapeutic development of treatment in this field.