Assessing the impact of cGAS-STING pathway activation on adoptive cell therapy using a patient-derived 3D ex vivo tumor organoid model

Abstract

Introduction: Adoptive cell therapy (ACT) with ex vivo expanded tumor infiltrating lymphocytes (TILs) has been of growing interest in the treatment of solid tumors. It is critical to develop effective combination therapies to overcome intrinsic immune escape mechanisms limiting the efficacy of ACT in individual tumors. Stimulation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway results in the expression of pro-inflammatory genes which can result in activation of multiple immune cells promoting innate immunity in addition to senescence of cancer cells. Here we analyzed the efficacy of cGAS-STING pathway activation alone and in combination with a PD-1 inhibitor nivolumab on activation and infiltration of TILs in the 3D tumor organoids.