How do MSI status and tumor mutational burden guide immunotherapy selection?

How do MSI status and tumor mutational burden guide immunotherapy selection?

• A. Only BRCA status matters for immunotherapy
• B. MSI-H/dMMR tumors and high tumor mutational burden predict better response to immune checkpoint inhibitors
• C. They are biomarkers for chemotherapy response
• D. They do not guide therapy

Answer: (B)

The main idea is that MSI status and tumor mutational burden are biomarkers that help predict how well a tumor will respond to immune checkpoint inhibitors. When microsatellite instability is high due to deficient mismatch repair, tumors accumulate a large number of mutations, creating many neoantigens. This makes cancer cells more recognizable to the immune system, so checkpoint inhibitors are more likely to unleash an effective T-cell attack in these tumors. Similarly, a high tumor mutational burden means more mutations and more neoantigens, which again increases the chance that T cells will detect and attack the cancer when the immune brakes are released by therapy. These biomarkers guide immunotherapy because they reflect how “visible” the tumor is to the immune system. They are not perfect predictors—some MSI-H or high-TMB tumors don’t respond, and some tumors without these features can respond—but they are the best-supported signals for choosing immune checkpoint blockade across many cancer types. In short, MSI-H/dMMR status and high TMB are associated with better responses to immune checkpoint inhibitors, making them helpful in selecting patients for these therapies.

The main idea is that MSI status and tumor mutational burden are biomarkers that help predict how well a tumor will respond to immune checkpoint inhibitors. When microsatellite instability is high due to deficient mismatch repair, tumors accumulate a large number of mutations, creating many neoantigens. This makes cancer cells more recognizable to the immune system, so checkpoint inhibitors are more likely to unleash an effective T-cell attack in these tumors. Similarly, a high tumor mutational burden means more mutations and more neoantigens, which again increases the chance that T cells will detect and attack the cancer when the immune brakes are released by therapy.

These biomarkers guide immunotherapy because they reflect how “visible” the tumor is to the immune system. They are not perfect predictors—some MSI-H or high-TMB tumors don’t respond, and some tumors without these features can respond—but they are the best-supported signals for choosing immune checkpoint blockade across many cancer types. In short, MSI-H/dMMR status and high TMB are associated with better responses to immune checkpoint inhibitors, making them helpful in selecting patients for these therapies.