Abstract A029: Preferential ability of IL-7 versus IL-2 to restore effector T cell responses in the presence of regulatory T cells assessed using MR-MCTM assays <i>in vitro</i>

Abstract Within the tumour microenvironment, regulatory T cells diminish anti-tumour responses by inhibiting effector T cell activation. Immunotherapies that enhance the effector T cell response may also enhance Treg activity, limiting the overall action of the therapy. It is therefore important to consider the ‘net-effect’ of immune activation in systems containing both cell types. To better understand responder T cell activation in a relevant cellular environment, we have investigated human effector T cell activation in the presence of regulatory T cells in vitro exploiting multiple readouts from multi-cell type suppression assays (MR-MCTM suppression assay). These assays have been performed in the absence or presence of IL-2 (hypothesised to boost both effector and regulatory T cell responses), and the absence or presence of IL-7 (hypothesised to skew towards effector T cell responses), to assess potential for biased activation of effector T cells over regulatory T cells. For certain activation markers, e.g. CD25 and CD71, the ability to restore effector T cell expression in the presence of regulatory T cells was greater for IL-7 compared to IL-2. We have also investigated the impact of these two cytokines on a range of early and later activation readouts of the responder T cell populations to add granularity to overall impact. Interestingly and in contrast to IL-7, IL-2 evoked greater increases in activation marker expression by regulatory T cells, indicating enhanced regulatory T cell function may contribute to the differential impact of these cytokines upon the responder T cell response. These results demonstrate how potential immunotherapies may differentially impact effector and regulatory T cell populations and highlight the considerable utility of investigating potential immunotherapies (e.g. checkpoint inhibitors) in MR-MCTM assays to better understand impact upon the overall balance of immune activation. Citation Format: Emma Welsh, Zhi Li, Leila Sallie, Ashley Pegg, Hujo Chan, Jamie Cowley, Arshpreet Kaur, Neale Harrison, David J Smith, Mark Bryant, Catherine A Brady, John Gordon, Nicholas Barnes, Omar Qureshi. Preferential ability of IL-7 versus IL-2 to restore effector T cell responses in the presence of regulatory T cells assessed using MR-MCTM assays in vitro [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A029.