Microsatellite instability (MSI-H) in colorectal cancer, classically seen in Lynch syndrome, results from defective mismatch repair (MMR). How does MSI-H status influence cancer immunotherapy response?

• A MSI-H tumors are resistant to checkpoint inhibitors because neoantigen load is low
• B MSI-H tumors respond poorly to anti-VEGF therapy
• C MSI-H status predicts response to EGFR-targeted therapy in colorectal cancer
• D MSI-H tumors have high tumor mutational burden with abundant neoantigens, predicting response to PD-1/PD-L1 checkpoint blockade ✓

Explanation

MSI-H tumors accumulate thousands of somatic mutations due to defective MMR, generating a high tumor mutational burden (TMB-H) and abundant immunogenic neoantigens. This creates a pre-existing immune response that is held in check by PD-1/PD-L1 inhibitory pathways. Pembrolizumab (anti-PD-1) received the first tumor-agnostic FDA approval for MSI-H/dMMR cancers. MSI-H actually predicts favorable response to checkpoint blockade; KRAS mutation (not MSI) predicts resistance to EGFR therapy.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.