Abstract Adoptive cell therapy has the potential to increase antitumor immunity by modifying cells in-vitro to expand lymphocytes that recognize and attack the tumor. The functional capacity and survival of the cells transferred to the patient heavily depends on the memory subpopulations that are being expanded in the laboratory, hence, obtaining early memory cells is desirable. The main objective of our work was to determine a strategy for in-vitro expansion of human stem cell-like memory T CD4 lymphocytes. Starting from naive cells, stimulated with a polyclonal agent supplemented with different combinations of cytokines from the common gamma family, we found that the combination of IL-7, IL-15 and IL-21 or IL-7 and IL-21 were the cocktails that produced a greater number of cells with a stem memory phenotype, measured by flow cytometry. Additionally, through the measurement of membrane proteins and in-silico analysis, a close relationship between stem cell-like memory and the follicular helper T cells differentiation program was established, which we believe contributes to a better understanding of the processes that underlie the generation and maintenance of memory and, therefore, may improve current strategies of expansion of T cells for immunotherapy purposes.