FIGURE 2.

ACT-derived T cell products and cross-talk with pre-existing memory/Ag-experienced subsets (the good, the bad, and the ugly neighbors). (A) During in vivo Ag priming or in vitro engineering/expansion, T_N acquire diverse phenotypes, reflecting various degrees of differentiation (T_CM, T_EM, T_EFF, T_RM, T_EX, and T_reg). Each subset reveals defined requirements for proper effector function and survival. (B) In the context of ACT, newly infused T cells will interact with pre-existing subsets, and either benefit from good memory subsets or take advantage of them (T_CM, T_EM, T_EFF, and T_RM) in promoting therapeutic anti-tumor responses (green arrows) or be inhibited by nasty ones (T_EX and T_reg). In some cases, competing for nutrients/survival signal (Figure 1) might also dim ACT efficacy (red arrows). Putative collaborative and antagonistic relationship between pre-existing memory subsets and ACT cell products are depicted.