Functional Genome Profiling to Understand Cancer Immune Responsiveness

It has been almost two decades since we first proposed the use of minimally invasive serial biopsies to dissect the biology underlining cancer immune responsiveness (CIR) by looking for predictors of response, understanding mechanisms of action (MOA) of therapeutics and documenting strategies adopted by tumor cells to escape immune recognition. This approach led to the first description in 2002 of predictors of CIR, the characterization of the pharmacodynamics of several immune therapeutics, and the geneses of immune escape under immunological pressure prompted by successful treatment. The presumption was straightforward; study CIR where it occurs: the target organ. Since then, a large number of studies corroborated these early observations adding sophistication and accuracy to the investigations. Here, we summarize the history of functional genomic profiling as a discovery and validation tool for immune oncology (IO) and new insights that could be derived by single novel technologies.