Extensive manipulation, mechanical force, and labelling methods used to enrich cells activate transcriptional programs that mask molecular profiles truly significant to any underlying disease. The consequence is identification of drug targets that are not relevant to the biological process under study. Based on Nakhoda and Olszanski, 2022 (Addressing Recent Failures in Immuno-Oncology Trials to Guide Novel Immunotherapeutic Treatment Strategies), lack of an optimal biomarker is one of the main challenges to clinical trial success. This represents a huge loss for both industry and the advance of medicine.