Stem-like T cells and niches: Implications in human health and disease

Abstract

Recently, accumulating evidence has elucidated the important role of T cells with stem-like characteristics in long-term maintenance of T cell responses and better patient outcomes after immunotherapy. The fate of TSL cells has been correlated with many physiological and pathological human processes. In this review, we described present advances demonstrating that stem-like T (TSL) cells are central players in human health and disease. We interpreted the evolutionary characteristics, mechanism and functions of TSL cells. Moreover, we discuss the import role of distinct niches and how they affect the stemness of TSL cells. Furthermore, we also outlined currently available strategies to generate TSL cells and associated affecting factors. Moreover, we summarized implication of TSL cells in therapies in two areas: stemness enhancement for vaccines, ICB, and adoptive T cell therapies, and stemness disruption for autoimmune disorders.

Postinfusion PD-1+ CD8+ CAR T cells identify patients responsive to CD19 CAR T-cell therapy in non-Hodgkin lymphoma

“…Overall, these PD-1 + TIM3 + T-bet + GZMB + cells had an expression pattern similar to previously described CD8 + effector-like transitory T cells. 22 , 23 , 24 , 25 , 26 , 31 Clusters 7 and 13, also increased in the CR cohort, were PD-1 + , TCF1 low , and Thymocyte selection-associated high mobility group box protein (TOX) − with a diverse expression of EOMES and CD28 and appeared to be in transition from stem-like to effector-like transitory cells. On the other hand, clusters 2, 3 and 4, increased in the PD group, were T-bet + GZMB + , but PD-1 - .…”

“…Clusters 8 and 9, increased in the CR cohort, were PD-1 + TCF1 + T-box expressed in T cells (T-bet) − , which is consistent with the phenotype of stem-like T cells. 22 , 23 , 24 , 25 , 26 These clusters also had high expression of other stem-like T-cell markers such as CD28 and Eomesodermin (EOMES). 22 , 23 , 24 , 25 , 26 Clusters 11 and 12, increased in the CR group, were PD-1 + TIM3 + , and expressed high levels of effector T-cell markers including Granzyme B (GZMB) and T-bet.…”

“… 22 , 23 , 24 , 25 , 26 These clusters also had high expression of other stem-like T-cell markers such as CD28 and Eomesodermin (EOMES). 22 , 23 , 24 , 25 , 26 Clusters 11 and 12, increased in the CR group, were PD-1 + TIM3 + , and expressed high levels of effector T-cell markers including Granzyme B (GZMB) and T-bet. Overall, these PD-1 + TIM3 + T-bet + GZMB + cells had an expression pattern similar to previously described CD8 + effector-like transitory T cells.…”

“…We found that the presence of postinfusion Programmed cell death protein 1 (PD-1) + CD8 + CAR-Ts was highly associated with achievement of CR by 6 months. Further analysis identified multiple subtypes of PD-1 + CD8 + CAR-Ts that correlated with improved clinical outcomes, including PD-1 + T cell factor 1 (TCF1) + stem-like CAR-T cells, 22 , 23 , 24 , 25 , 26 and PD-1 + T-cell immunoglobulin and mucin-domain containing-3 (TIM3) + effector-like CAR-T cells. Additionally, we identified a subset of CD8 + CAR + T cells with effector-like function that was increased in patients who achieved a CR and had severe ICANS.…”

T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications

“…T SCM and T cells both increased in patients with HIV after antiretroviral therapy ( 200 ). Stem cell-like T cells express CD62L, CCR7, TCF1, and LEF1 and can rapidly secrete IFN-γ, IL-2, and TNFα ( 201 , 202 ). Increasing the expression of stemness-related genes can induce pluripotent stem cell-like T cells.…”