CD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection.

ABSTRACT: The ability of focal radiotherapy to promote priming of tumor-specific CD8⁺ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radioth

SUBMITTER: Wennerberg E 

PROVIDER: S-EPMC7125001 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature