In addition, IL-21 has been shown to be an essential component of the CD4 + T cell help in sustaining the CD8 + T cell response during chronic, but not acute, lymphocytic choriomeningitis virus (LCMV) infections 14, 15, 16. Recent studies have shown that programming activated T cells with IL-21 in vitro facilitates the generation of human memory stem-like T cells and improves adoptive immunotherapy 11, 12, 13. More importantly, tumor-reactive T cells generated under the influence of IL-21 show a superior antitumor effect in vivo compared to T cells grown in other γc cytokines 8, 10. IL-21 acts synergistically with IL-7 or IL-15 to promote proliferation and survival of both memory and naïve CD8 + T cells 9. Compared to IL-2, IL-21 plays a key role in the development and maintenance of memory CD8 + T cells through the induction of an early differentiation phenotype 8. ![]() IL-2 has been widely used to activate and expand T cells in vitro for adoptive immunotherapy. In this respect, the γ c family cytokines, especially IL-2, IL-15, and IL-21, play an important role in regulating the magnitude and function of CD8 + T cell response 7. A substantial effort is currently underway to identify the factors that determine the therapeutic efficacy of PD-1 blockade and to develop combination therapeutic approaches to increase patient response rates 4, 5, 6.Īs our understanding of the response or resistance to PD-1 blockade continues to evolve, it is generally recognized that successful antitumor immune responses following PD-1 blockade require reactivation and proliferation of antigen-experienced CD8 + T cells present in the tumor microenvironment (TME) 4. ![]() PD-1 blockade, which reinvigorates the tumor-reactive CD8 + T cells by removing the inhibition induced by the interaction of PD-1 and PD-L1, has achieved high success in mediating complete, durable responses in patients with advanced or conventional therapy-resistant cancers however, the successes are unfortunately limited to a minority of patients 1, 2, 3.
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