| Autor: |
Xu, Nuo, Palmer, Douglas C., Robeson, Alexander C., Shou, Peishun, Bommiasamy, Hemamalini, Laurie, Sonia J., Willis, Caryn, Dotti, Gianpietro, Vincent, Benjamin G., Restifo, Nicholas P., Serody, Jonathan S. |
| Zdroj: |
The Journal of Experimental Medicine; February 2021, Vol. 218 Issue: 2 pe20200844-e20200844, 1p |
| Abstrakt: |
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 the activity of CAR T cells using an orthotopic model of locally advanced breast cancer. CAR T cells generated from Th/Tc17 cells given with the STING agonists DMXAA or cGAMP greatly enhanced tumor control, which was associated with enhanced CAR T cell persistence in the TME. Using single-cell RNA sequencing, we demonstrate that DMXAA promoted CAR T cell trafficking and persistence, supported by the generation of a chemokine milieu that promoted CAR T cell recruitment and modulation of the immunosuppressive TME through alterations in the balance of immune-stimulatory and suppressive myeloid cells. However, sustained tumor regression was accomplished only with the addition of anti–PD-1 and anti–GR-1 mAb to Th/Tc17 CAR T cell therapy given with STING agonists. This study provides new approaches to enhance adoptive T cell therapy in solid tumors. |
| Databáze: |
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