Immunotherapy and patients treated for cancer with microsatellite instability

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Microsatellite instability (MSI) arises from DNA mismatch repair gene defects, leading to a distinct tumor phenotype.
• This phenotype is observed across various cancers, including colorectal, endometrial, and gastric neoplasms.
• MSI tumors are known for significant immune cell infiltration and a high neo-antigen load.

Purpose of the Study:

• To provide a comprehensive overview of the MSI phenotype, including its biological characteristics and diagnostic approaches.
• To examine the role of MSI as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy response.
• To focus on MSI's predictive value in both colorectal and non-colorectal solid tumors.

Main Methods:

• Literature review and synthesis of existing research on MSI.
• Analysis of diagnostic methods for identifying MSI.
• Evaluation of clinical data and studies on ICI efficacy in MSI-positive tumors.

Main Results:

• MSI is linked to specific genetic alterations in DNA mismatch repair genes.
• MSI tumors exhibit a high degree of immunogenicity due to neo-antigens.
• Evidence supports MSI as a biomarker for predicting response to immune checkpoint inhibition.

Conclusions:

• MSI is a crucial factor in understanding tumor biology and immune response.
• MSI testing is valuable for identifying patients likely to benefit from immune checkpoint inhibitors.
• The predictive role of MSI extends across various solid tumor types, including colorectal cancer.