Figure 2. Functional attributes of physiological and synthetic T cell states. This figure illustrates the distinct phenotypic and functional characteristics of three specialized T cell states. Plus signs indicate robustness of the designated function, minus signs indicate the absence of the function. Left: The first state, TSCM, is marked by the expression of the transcription factor TCF7 and the repression of the ZEB2. TSCM are identifiable by surface markers CD62L and CCR7, associated with their migratory capacity to lymphoid tissues. These cells are characterized by their ability to proliferate and persist without exerting effector functions, displaying high efficacy in adoptive transfer therapies. Center: The second state, T effector cells (TEFF), represents a terminally differentiated phenotype where TCF7 expression is silenced and ZEB2 is active. TEFF are distinguished by the surface expression of CX3CR1 and the production of cytotoxic granules, indicative of their effector functions. Despite their potent killing capacity, TEFF exhibit limited proliferation, persistence, and are less effective therapeutically upon adoptive transfer due to their short-lived nature. Right: The third hypothetical state described here by Wang et al. (2024) is a novel synthetic state designated as TIF, which purportedly combines the attributes of both TSCM and TEFF. This state is hypothesized to arise from the knockout (KO) of BCOR and ZC3H12A. According to Wang et al. (2024), TIF cells simultaneously maintain TCF7 and ZEB2 expression, bear stem-like and effector cell markers, and possess the ability to proliferate, persist, and execute effector functions, potentially offering a synergistic therapeutic advantage.