Stem cell-like memory T cells: Role in viral infections and autoimmunity

Table 1 Summary of approaches to target memory stem cells in different disease conditions

No.	Disease	Approach	Target molecules	Ref.
1	HIV-1 infection	Ex vivo expansion of CD8+ TSCM cells with IL-7 & IL-15 with CD3/CD28	T cell receptor	[46]
2	Immunodeficiency, tumor	Ex vivo expansion of CD8+ TSCM cells with urolithin A	Pink-1 mediated mitophagy. Dephosphorylation of β-catenin through action of Wnt signaling	[61]
3	Tumors and malignancies	Use of TSCM-like CAR-T cells (particularly CAR modified CD8+ T cells)	Various tumor/lymphoma antigens	[65-67,69]
4	Chronic viral infections	Increased survival of CD8+ TSCM through Wnt agonists	Increased expression of TCF1	[64]
5	HIV-1 infection	Nanoparticles or aptamers targeting latent reservoirs by inducing differentiation of TSCM cells to effector memory subsets	Key molecules of Wnt-β-catenin pathway	[1]
6	HIV-1 infection	Shock and kill strategy to reactivate HIV from CD4+ TSCM cells with LRAs + TLR agonists to activate CD8+ T cells	Killing of activated reservoirs by cytotoxic T cells	[76]
7	HIV-1 infection	Block and Lock strategy by HIV Tat inhibitors	No HIV replication by blocking of HIV promoter	[77]
8	Autoimmune diseases	Nanoparticles or siRNA to suppress TSCM cells	Inhibition of key molecules of NF-κB signaling	[79,80]
9	Autoimmune diseases	Wnt agonists or shRNA or inhibitors such as PRI-724 to disrupt TSCM cells by inducing differentiation to EM cells	TCF7, CBP/β-catenin pathway	[1,81]
10	Autoimmune diseases	Induced differentiation of TSCM cells to short lived EM cells	Molecules of mTOR/AMPK pathway	[1]
11	Type-1 diabetes	Selective inhibition of metabolic machinery of TSCM cells	Decreased glucose metabolism through inhibition of GLUT1	[5]
12	Type-1 diabetes	Antibodies to block CCR7 to target TSCM cells	CCR7	[86]

HIV-1: Human immunodeficiency virus-1; GLUT1: Glucose transporter 1; T_SCM: Stem cell-like memory T; CAR: Chimeric antigen receptor; CBP: Cyclic AMP-response element-binding protein-binding protein; LRA: Latency reversal agents; EM cell: Effector memory; TLR: Toll-like receptor.