Table 2.

Recently reported γc family cytokines or responding receptor engineered for transferred T cells stemness

Publication	Year		γc family cytokines	Engineered version	Discovery
Mo F et al. [76]	2021		IL-2	H9T, an engineered IL-2 partial agonist.	The H9T sustained the stemness of TCR-T and CAR-T cells through altered STAT5 signaling, mediating robust antitumor activity in vivo.
Aspuria PJ.et al. [79]	2021		IL-2	Orthogonal IL-2/IL-2Rβ pair, an orthogonal human IL-2 (STK-009) selectively pairs with an orthogonal human IL-2Rβ (hoRb) expressed on CAR T cells.	STK-009 expanded hoRb-expressing CAR T cells and maintained the presence of TSCM.
Kalbasi A et al. [10]	2022		IL-2 and IL-9 receptors	Orthogonal IL-2-O9R pair, IL-2Rβ-ECD-IL-9R-ICD (o9R), the chimeric receptor that orthogonal IL-2 receptor extracellular domain was fused with the intercellular domain of IL-9.	Co-culture of o9R-transduced pmel TCR-T cells with specific oIL-2 upregulated T cell stemness genes resulted in fantastic tumor eradication for ACT.
Hurton LV et al. [116]	2016		IL-15	mbIL-15, the mbIL15-CAR T cells co-expressing CAR with a membrane-bound chimeric IL-15 to incorporate the costimulatory properties of IL-15.	The mbIL-15 instructed CAR-T cells to possess a memory stem cell-like transcriptional profile and developed stemness attributes.
Guo J. et al. [123]	2021		IL-15	pro-IL-15, a next-generation IL-15 with the extracellular domain of IL-15Rβ fused to the N-terminus of super-IL-15-Fc (IL-15 fused with the IL-15Rα sushi domain) through a tumor-enriched Matrix Metalloproteinase (MMP) cleavable peptide linker to block its activity.	The pro-IL-15 specifically promoted stem-like CD8(+) T cells including infused T cells inside the TME making it possible to expand and persist of infused TSCM in TME.
Li Y. et al. [130]	2021		IL-21	The fusion protein PD-1Ab21 by fusion of IL-21 to anti-PD-1antibody can be targeted to tumor-reactive T cells.	PD-1Ab21 promoted TSCM generation and showed impressive antitumor effects.