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Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic
Strategy for Breast Cancer
#MMPMID29914097
Mostafa AA
; Meyers DE
; Thirukkumaran CM
; Liu PJ
; Gratton K
; Spurrell J
; Shi Q
; Thakur S
; Morris DG
Cancers (Basel)
2018[Jun]; 10
(6
): ? PMID29914097
show ga
As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited,
exploration of OVs as part of a broader immunotherapeutic treatment strategy for
cancer is necessary. Here, we investigated the ability for immune checkpoint
blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of
breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed
in human and murine BrCa cell lines following RV exposure. Furthermore,
RV-induced upregulation of tumor cell PD-L1 was evaluated. In vivo, the
immunocompetent, syngeneic EMT6 murine model of BrCa was employed to determine
therapeutic and tumor-specific immune responses following treatment with RV,
anti-PD-1 antibodies or in combination. RV-mediated oncolysis and cytokine
production were observed following BrCa cell infection and RV upregulated tumor
cell expression of PD-L1. In vivo, RV monotherapy significantly reduced disease
burden and enhanced survival in treated mice, and was further enhanced by PD-1
blockade. RV therapy increased the number of intratumoral regulatory T cells,
which was reversed by the addition of PD-1 blockade. Finally, dual treatment led
to the generation of a systemic adaptive anti-tumor immune response evidenced by
an increase in tumor-specific IFN-γ producing CD8? T cells, and immunity
from tumor re-challenge. The combination of PD-1 blockade and RV appears to be an
efficacious immunotherapeutic strategy for the treatment of BrCa, and warrants
further investigation in early-phase clinical trials.
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