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 radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of cytotoxic T-lymphocyte–associated protein 4 blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2020
- Source ID
- 10.1158/2326-6066.cir-19-0449
Entities
People
- Claire Lhuillier
- Erik Wennerberg
- Fengli Zhang
- Nils-petter Rudqvist
- Qiuying Chen
- Sandra Demaria
- Sheila Spada
- Silvia C. Formenti
- Steven S. Gross
- Sylvia Gruber
- Xi Kathy Zhou
Organizations
- National Institutes of Health
- The Breast Cancer Research Foundation
- United States Department of Defense
- Weill Cornell Medicine