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

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Date
2020-04
ICR Author
Wennerberg, Erik
Author
Wennerberg, E
Spada, S
Rudqvist, N-P
Lhuillier, C
Gruber, S
Chen, Q
Zhang, F
Zhou, XK
Gross, SS
Formenti, SC
Demaria, S
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Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/4092
DOI
https://doi.org/10.1158/2326-6066.cir-19-0449
Collections
  • Radiotherapy and Imaging
Subject
Dendritic Cells
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Animals
Mice, Inbred BALB C
Mice, Knockout
Humans
Mice
Neoplasms
5'-Nucleotidase
Interferon Type I
Adenosine
Female
Research team
Radiation-enhanced Immunotherapy
Language
eng
Date accepted
2020-02-04
License start date
2020-04
Citation
Cancer immunology research, 2020, 8 (4), pp. 465 - 478

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