STING agonist promotes CAR T cell trafficking and persistence in breast cancer

• DOI: 10.1084/jem.20200844
• Publication Date: 2020-12-31T14:41:09Z
• Authors: Nuo Xu; Douglas C. Palmer; Alexander C. Robeson; Peishun Shou; Hemamalini Bommia...; Sonia J. Laurie; Caryn Willis; Gianpietro Dotti; Benjamin G. Vincent; Nicholas P. Restifo; Jonathan S. Serody
• Keywords: 0303 health sciences; Receptors, Chimeric Antigen; T-Lymphocytes; Membrane Proteins; Breast Neoplasms; 3T3 Cells; Immunotherapy, Adoptive; Article; Cell Line; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Antigens, Neoplasm; Tumor Microenvironment; Animals; Female; Chemokines

CAR T therapy targeting solid tumors is restrained by limited infiltration and persistence of those cells in the tumor microenvironment (TME). Here, we developed approaches to enhance activity using an orthotopic model locally advanced breast cancer. generated from Th/Tc17 given with STING agonists DMXAA or cGAMP greatly enhanced control, which was associated cell TME. Using single-cell RNA sequencing, demonstrate that promoted trafficking persistence, supported generation a chemokine milieu recruitment modulation immunosuppressive TME through alterations balance immune-stimulatory suppressive myeloid cells. However, sustained regression accomplished only addition anti-PD-1 anti-GR-1 mAb agonists. This study provides new adoptive tumors.