There are still many unknowns with the CD8HTM and CD28HTM CARs, including the kinetics of synapse formation, how the synapse is ordered, if there are differences in proximal signaling, how receptor endocytosis and recycling compare, what signals are promoting the difference in granzyme B production, and how are these CAR-T cells behaving within the tumor. This evidence concerns the gene GZMB and neoplasm.