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Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Open accessAbstract
High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death-ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 was upregulated in the tumor microenvironment after IR. Administration of anti-PD-L1 enhanced the efficacy of IR through a cytotoxic T cell-dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti-PD-L1 synergistically reduced the local accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which suppress T cells and alter the tumor immune microenvironment. Furthermore, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and radiotherapy.
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Metadata
- Authors
- Deng, L., Liang, H., Burnette, B., Beckett, M., Darga, T., Weichselbaum, R. R., & Fu, Y.-X.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-01-02
- Volume
- 124
- Issue
- 2
- Pages
- 687-695
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2052727153
- Cited by
- 2,105
- References
- 16
- FWCI
- 60.75
- Type
- journal article
- Language
- en
- Open access
- green
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