Virotherapy induces massive infiltration of neutrophils in a subset of tumors defined by a strong endogenous interferon response activity.

Abstract:

:Oncolytic virotherapy has shown substantial promises as an alternative therapeutic modality for solid tumors in both preclinical studies and clinical trials. The main therapeutic activity of virotherapy derives from the direct lytic effect associated with virus replication and the induction of host immune responses to the infected tumor cells. In this study, we show that some human and murine tumor cell lines are highly resistant to the lytic effect of a type II herpes simplex virus-derived oncolytic virus, FusOn-H2, which was constructed by deleting the N-terminal region of the ICP10 gene. However, these tumor cells still respond exceptionally well to FusOn-H2 virotherapy in vivo. Histological examination of the treated tumors revealed that, in contrast to tumors supporting FusOn-H2 replication, implants of these highly resistant lines showed massive infiltration of neutrophils after virotherapy. Further analysis indicated a correlation between an intrinsically strong interferon response activity and the recruitment of neutrophils in these tumors. These results suggest that an innate immune response mainly represented by neutrophils in these tumors may be part of the virotherapy-mediated antitumor mechanism.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Fu X,Tao L,Rivera A,Xu H,Zhang X

doi

10.1038/cgt.2011.46

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

785-94

issue

11

eissn

0929-1903

issn

1476-5500

pii

cgt201146

journal_volume

18

pub_type

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