Functional Genome Profiling to Understand Cancer Immune Responsiveness

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Minimally invasive serial biopsies were proposed nearly two decades ago to study cancer immune responsiveness (CIR).
• Early work identified CIR predictors, characterized therapeutic pharmacodynamics, and elucidated immune escape mechanisms.
• Subsequent research has validated and refined these initial findings.

Purpose of the Study:

• To summarize the historical application of functional genomic profiling in immune oncology (IO).
• To highlight the role of serial biopsies in understanding CIR, therapeutic MOA, and immune escape.
• To present new insights from emerging single-cell technologies.

Main Methods:

• Utilizing minimally invasive serial biopsies to analyze CIR directly within the tumor microenvironment.
• Employing functional genomic profiling to identify response predictors and mechanisms of action.
• Integrating data from multiple biopsies over time to track dynamic biological changes.

Main Results:

• Established early predictors of CIR in 2002.
• Characterized the pharmacodynamics of various immune therapeutics.
• Documented tumor cell strategies for immune escape under treatment pressure.

Conclusions:

• Minimally invasive serial biopsies are a powerful tool for dissecting cancer immunology.
• Functional genomic profiling has been crucial for discovery and validation in IO.
• Novel technologies promise further advancements in understanding and treating cancer immunity.