What are the two or three critical issues facing the field of cancer immunotherapy?
The lesson of the past decade is that tumor biology (PD-L1 expression, CD8 infiltrates, TLS, TMB, …) drives the efficacy of checkpoint targeted immunotherapies, not the tumor histology. Accordingly, what drives the resistance to such treatments (genomic instability, high VEGF, Tregs, IL6/8,…) is also vastly histology independent. Therefore, one of the biggest challenges is to disrupt the conventional oncology taxonomy in order to treat patients according to the biology of their disease rather than its histological description. The practical consequence of this paradigm shift is the need to develop new treatments according to drug target expression or biomarkers rather than per historical indication. This would also require the field to have biomarkers or target screening assays with short turnaround times in order to enroll patients in trials based on their actual disease biology rather than their archival material.