Synthetic IL-21 cytokine mimetic promotes T cell function

Synthetic cytokine mimetics of IL-2 have been developed, including neoleukin-2 (Neo2), which has been shown to have enhanced therapeutic efficacy over IL-2, with reduced toxicity. IL-21 has also been used in TIL therapy to promote T cell expansion. Here, we tested the efficacy of Neo2, native IL-21, or synthetic IL-21 (21h10) in treating mice bearing B16 tumors that received ACT with melanoma-specific T cells (TRP1High and TRP1Low ; TCRs recognizing antigen with high or low affinity). We performed single-cell RNA-sequencing on these tumors to analyze cytokine therapy-induced changes in the microenvironment. Overall design: Two days prior to tumor inoculation, naïve melanoma-specific T cells (TRP1High and TRP1Low) were adoptively transferred to wild-type mice. B16 tumors were inoculated and 5 days post tumor inoculation I.P. cytokine treatments commenced every day until day 15 when tumors from each cohort were labelled with hashtag antibodies and subjected to single-cell RNA-sequencing.