Abstract：
:Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with local interleukin-12 (IL-12) microsphere (MS) immunotherapy results in marked tumor reduction and cures in multiple preclinical mouse models of PDA. Our findings demonstrate an increase of intratumoral interferon gamma (IFNγ) production following SBRT/IL-12 MS administration that initiates suppressor cell reprogramming and a subsequent increase in CD8 T cell activation. Furthermore, SBRT/IL-12 MS therapy results in the generation of systemic tumor immunity that is capable of eliminating established liver metastases, providing a rationale for follow-up studies in advanced metastatic disease.
journal_name
Cell Repjournal_title
Cell reportsauthors
Mills BN,Connolly KA,Ye J,Murphy JD,Uccello TP,Han BJ,Zhao T,Drage MG,Murthy A,Qiu H,Patel A,Figueroa NM,Johnston CJ,Prieto PA,Egilmez NK,Belt BA,Lord EM,Linehan DC,Gerber SAdoi
10.1016/j.celrep.2019.08.095subject
Has Abstractpub_date
2019-10-08 00:00:00pages
406-421.e5issue
2issn
2211-1247pii
S2211-1247(19)31157-Xjournal_volume
29pub_type
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