Finding the hot spot: identifying immune sensitive gastrointestinal tumors

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, offering durable responses in metastatic solid tumors.
• ICBs are monoclonal antibodies targeting immune evasion molecules like PD-1 and CTLA-4.

Purpose of the Study:

• To review current evidence on predictive biomarkers for ICB response in gastrointestinal (GI) tumors.
• To identify established and emerging biomarkers for optimizing immunotherapy in GI malignancies.

Main Methods:

• Systematic literature review of FDA-approved drugs and therapies.
• Searches included NCI drug lists, FDA website, and major oncology conference proceedings (AACR, ASCO, ESMO 2019).
• PubMed search utilized MeSH terms: biomarkers, immunotherapy, gastrointestinal diseases, and neoplasms.

Main Results:

• Microsatellite instability (MSI) is the most potent predictive biomarker, particularly in colorectal cancer.
• Programmed death-ligand 1 (PD-L1) shows predictive value in gastroesophageal malignancies.
• Tumor mutational burden-high (TMB-H) is a potential biomarker in anal and biliary tract carcinomas, independent of MSI.

Conclusions:

• MSI demonstrates the strongest predictive power for ICB response in GI cancers.
• Ongoing research explores novel biomarkers, including the microbiome and RNA-editing mutations.
• Future strategies may involve combination therapies targeting complementary pathways to PD-1/PD-L1 axis inhibition.